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Objective Patients with lupus erythematosus (LE) are at heightened risk for clinical events, chiefly heart attacks and strokes, from atherosclerotic cardiovascular disease (ASCVD). We recently proposed new guidelines to assess and manage ASCVD event risk specifically in LE. Here, we examined current cardiovascular management in light of these new recommendations.Methods We studied our entire UPenn Longitudinal Lupus Cohort of patients with cutaneous LE, without (CLE-only) or with (CLE+SLE) concurrent systemic LE, for whom we had full access to medical records (n=370, LE-ASCVD Study Cohort).Results Of our LE-ASCVD Study Cohort, 336 out of 370 (90.8%) had a designated primary-care physician. By the new guidelines, the most recent low-density lipoprotein (LDL) levels were above-goal for 249 out of 370 (67.3%). Two-hundred sixty-six (71.9%) had hypertension, which was undertreated or untreated in 198 out of 266 (74.4%). Of current smokers, 51 out of 63 (81.0%) had no documented smoking cessation counselling or referrals. Diabetes and triglyceridaemia were generally well managed. Of the cohort, 278 qualified for two widely used online estimators of ASCVD event risk in primary prevention: the ACC-ASCVD Risk Estimator Plus and QRisk3. We also stratified these 278 patients into our recently defined categories of ASCVD event risk in LE. These three methods for estimating ASCVD event risk showed clinically meaningful discordance for 169 out of 278 (60.8%). The documented rate of ASCVD events in the first 10 years after enrolment was 13.5% (95% CI 8.9%, 17.9%), similar between CLE-only and CLE+SLE, indicating an at-risk population despite the preponderance of women and an average age at enrolment of only 47 years.Conclusion Patients with CLE-only or CLE+SLE are undertreated compared with the new guidelines and, accordingly, they experience a significant burden of ASCVD events. Moreover, it is unclear how to accurately assess their future ASCVD event risk, except that it is substantial. Efforts are underway to improve ASCVD event risk estimation and guideline implementation in patients with lupus.

Drug development in lupus has improved over the past 10 years but still lags behind that of other rheumatic disease areas. Assessment of prospective lupus therapies in clinical trials has proved challenging for reasons that are multifactorial including the heterogeneity of the disease, study design limitations and a lack of validated biomarkers which greatly impacts regulatory decision-making. Moreover, most composite outcome measures currently used in trials do not include patient-reported outcomes. Given these factors, the Addressing Lupus Pillars for Health Advancement Global Advisory Committee members who serve on the drug development team identified an opportunity to convene a meeting to facilitate information sharing on completed and existing outcome measure development efforts. This meeting report highlights information presented during the meeting as well as a discussion on how the lupus community may work together with regulatory agencies to simplify and standardise outcome measures to accelerate development of lupus therapeutics.

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

Cutaneous lupus erythematosus (CLE) is a disfiguring and potentially disabling disease that causes significant morbidity in patients. Antimalarials are an important class of medication used to treat this disease and have been the first-line systemic therapy since the 1950s. Quinacrine, in particular, is used as an adjuvant therapy to other antimalarials for improved control of CLE. Quinacrine is currently unavailable in the USA, which has taken away an important component of the treatment regimen of patients with CLE. This paper reviews the evidence of available local and systemic therapies in order to assist providers in choosing alternative treatments for patients who previously benefited from quinacrine therapy.

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

Bullous systemic lupus erythematosus (BSLE) is a rare blistering presentation of systemic lupus erythematosus, typically affecting women with the highest incidence in those of African descent. The key pathogenic insult includes the formation of autoantibodies against type VII collagen, which weaken the basement membrane zone and lead to the formation of subepidermal blisters. The acute vesiculobullous eruptions in BSLE generally tend to affect photo-distributed areas, although they can arise unrelated to sun exposure (eg, mucous membranes, axillae). The bullae can arise from erythematous macules, inflammatory plaques, or previously normal skin. Their appearance can range from small, grouped vesicles reminiscent of lesions in dermatitis herpetiformis to large, tense blisters, similar to bullous pemphigoid. Internal organ involvement occurs in up to 90% of those affected. This mostly includes lupus nephritis (classes III–V, lifetime prevalence of up to 90%), arthralgias/arthritis, and cytopenias, while serositis and neuropsychiatric involvement are rare. First-line management with dapsone should be considered in mild disease with stable underlying systemic lupus erythematosus. As discussed in this review, the off-label use of rituximab (an anti-CD20 B-cell depleting agent) has been shown to be safe and effective in several refractory cases of BSLE unresponsive to dapsone, glucocorticoids, or steroid-sparing immunosuppressants.

Many treatments are currently proposed for treating patients with bullous pemphigoid (BP). We assessed treatment modalities of BP depending on the different countries, BP extent, and patients’ comorbidities. We surveyed worldwide experts about how they treat patients with BP. A total of 61 experts from 27 countries completed the survey. Severe and moderate BP were treated with oral prednisone (61.4 and 53.7%, respectively) or superpotent topical corticosteroids (CSs) (38.6 and 46.3%, respectively). Conventional immunosuppressants were more frequently combined with oral prednisone (74.5%) than with superpotent topical CS (37.5%) in severe BP. Topical CSs were mainly used in Europe in mild (81.1%), moderate (55.3%), and severe (54.3%) BP. In the United States of America and Asia, systemic CSs were mainly proposed for treating severe (77.8 and 100%, respectively), moderate (70 and 77.8%, respectively), and also mild (47.1 and 33.3%, respectively) BP. Most experts reduced the initial dose of oral CS in patients with diabetes mellitus (48.1%) or cardiac insufficiency (40.2%) but rarely changed BP treatment in patients with neurological disorders or neoplasia. This survey showed major differences in the way patients with BP are treated between AmeriPac countries (United State of America, Latin America, and Australia) and Asia on the one hand and Europe and the Middle East on the other hand.

Cutaneous lupus erythematosus (CLE) is an autoimmune disease that can be associated with systemic lupus erythematosus (SLE) symptoms. The pathogenesis of both CLE and SLE is multifactorial, involving genetic susceptibility, environmental factors, and innate and adaptive immune responses. Despite the efficacy of current medications, many patients remain refractory, highlighting the necessity for new treatment options. Unfortunately, owing to challenges related in part to trial design and disease heterogeneity, only one new biologic in the last 50 years has been approved by the US Food and Drug Administration for the treatment of SLE. Thus, although SLE and CLE have a similar pathogenesis, patients with CLE who do not meet criteria for SLE cannot benefit from this advancement. This article discusses the recent trials and emphasizes the need to include patients with single-organ lupus, such as CLE, in SLE trials.

Abstract Background and rationale Ultraviolet-B (UVB) light induces dermal inflammation, although it is mostly absorbed in the epidermis. Recent reports suggest extracellular vesicles (EVs) act as a mediator of photodamage signaling. Melatonin is reported to be a protective factor against UV-induced damage. We hypothesized that EVs derived from UVB-irradiated keratinocytes might trigger proinflammatory responses in dermal cells and tested whether melatonin can ameliorate UVB-induced inflammation. Methods We used UVB-irradiated HaCaT cells, primary keratinocytes and STING knock-out mice to model production of EVs under photodamaging conditions and performed immunoblotting and ELISA to measure their effect on dermal macrophages. Results UVB-irradiated keratinocytes produce an increased number of EVs that contain higher concentrations of DNA and protein compared with controls. KC-derived EVs (KEVs) induced a STING- and inflammasome-mediated proinflammatory response in macrophages in vitro, and a pronounced inflammatory infiltrate in mouse dermis in vivo. Melatonin ameliorated KEVs inflammatory effect both in vitro and in vivo. Conclusions This data suggests EVs are mediators in a crosstalk that takes place between keratinocytes and their neighboring cells as a result of photodamage. Further studies exploring EVs induced by damaging doses of UVB, and their impact on other cells will provide insight into photodamage and may help develop targeted therapeutic approaches.

Background: Dermatomyositis (DM) is a rare autoimmune condition involving skin manifestations often resistant to standard treatments such as immunosuppressants and antimalarials. Biopsies show elevated inflammatory cells such as CD4+ T cells, dendritic cells, and cytokines. Lenabasum, a selective cannabinoid receptor 2 agonist, has demonstrated significant benefits in treating autoimmune skin diseases. Objectives: This study utilizes data from the open-label extension (OLE) phase of the lenabasum phase 2 trial and additional post-OLE follow-up data. Key aims include evaluating the drug’s long-term effectiveness and assessing disease manifestation recurrence. Methods: The phase 2 lenabasum trial enrolled patients with treatment-resistant, skin-predominant DM. The OLE consisted of a 3-year period during which 20 patients were on the drug for the entire duration, with assessments every 8 weeks to evaluate drug safety and efficacy. Subsequently, a follow-up retrospective chart review was performed on patients who completed the OLE as well as on control subjects with DM who did not participate in the lenabasum trial. Results: By week 68, patients exhibited reductions in Cutaneous Dermatomyositis Disease Area and Severity Index activity score (−21.8), Patient Skin Activity Visual Analog Scale (−3.0), and Skindex-29 (−28.0) from OLE baseline. After OLE, 58.3% maintained stable disease, significantly higher than controls (P = .035), with 41.7% not experiencing flares compared with 91.6% of controls. In addition, 50% of patients reported sustained pruritus improvement. Conclusions: Data from OLE and subsequent follow-up periods demonstrate lenabasum’s efficacy in maintaining disease stability, reducing flares, and improving DM symptoms, suggesting that it is a promising option for patients with treatment-resistant skin-predominant DM. Trial Registration: This study was registered at clinicaltrials.gov, with NCT02466243. Study registration was first submitted on June 2, 2015.

AbstractIntroduction Dermatomyositis, systemic and cutaneous lupus erythematosus have a significantly higher prevalence in women than men, emphasizing the relevance of exploring the relationship between sex hormones and autoimmune skin diseases. This review analyzes the interplay between sex hormones and these two skin diseases.Materials and methods We performed an extensive literature search using the PubMed database from July to August 2023. Search terms included ‘contraceptives’, ‘pregnancy’, ‘hormone replacement’, ‘tamoxifen’, and ‘aromatase inhibitors’.Results and Discussion This comprehensive literature review shows that there remains considerable debate regarding the use of hormonal contraceptives and hormonal replacement therapy in individuals with autoimmune skin conditions. Nonetheless, it is well established that their use is contraindicated in patients with antiphospholipid syndrome or when antiphospholipid antibodies are positive. Individuals experiencing disease flares and uncontrolled symptoms should also avoid these interventions. Pregnancy planning should be timed to coincide with well-managed disease states to minimize obstetric and neonatal complications. Hormonal breast cancer treatment requires close skin monitoring.Conclusion Pregnancy, menopause, contraceptive use, hormone replacement therapy, and breast cancer treatment drugs result in substantial shifts in hormone levels. Additionally, hormone levels are altered by aromatase inhibitors and anti-estrogen medications. These fluctuations can modulate mechanisms influencing autoimmune skin abnormalities.

Abstract 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-β cytokines were downregulated. IFN-γ and IFN-β 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

There have been a number of advances in the clinical and translational understanding of cutaneous lupus and dermatomyositis, which both disproportionately affect women. These advances have involved ongoing collaborations between dermatology and rheumatology that highlight the importance of the skin in these disorders, with improvement in the education of trainees and clinical management of these complex multisystem diseases. In addition, a new disease classification has allowed inclusion of patients with skin-predominant dermatomyositis, frequently associated with systemic findings, in the spectrum of idiopathic inflammatory myopathies. Validated outcome measures allow translational research and facilitate progress toward better and more targeted therapeutics. Clinical trials using disease severity tools, such as the Cutaneous Lupus Erythematosus Area and Severity Index and the Cutaneous Dermatomyositis Disease Area and Severity Index, allow measurement of improvement in the skin. Recent results of phase 2 and 3 trials clearly show that patients will benefit from collaborative interactions and studies between dermatology and rheumatology.

For patients with lupus erythematosus (LE) or dermatomyositis (DM), there is an urgent need to address a heightened risk of clinical events, chiefly heart attacks and strokes, caused by atherosclerotic cardiovascular disease (ASCVD). Patients with LE or DM frequently exhibit high levels of conventional risk factors for ASCVD events, particularly dyslipoproteinemia and hypertension; an amplified burden of atherosclerotic plaques; and increased age- and sex-adjusted rates of ASCVD events compared with the general population. The rate of ASCVD events exceeds what would be expected from conventional risk factors, suggesting that disease-specific autoimmune processes exacerbate specific, known pathogenic steps in atherosclerosis. Importantly, despite their heightened risk, patients with LE or DM are often undertreated for known causative agents and exacerbators of ASCVD. Herein, we propose an approach to assess and manage the heightened risk of ASCVD events in patients with LE or DM. Our approach is modeled in large part on established approaches to patients with diabetes mellitus or stage 3 or 4 chronic kidney disease, which are well-studied conditions that also show heightened risk for ASCVD events and have been explicitly incorporated into standard clinical guidelines for ASCVD. Based on the available evidence, we conclude that patients with LE or DM require earlier and more aggressive screening and management of ASCVD. We suggest that physicians consider implementing multipliers of conventional risk calculators to trigger earlier initiation of lifestyle modifications and medical therapies in primary prevention of ASCVD events, employ vascular imaging to quantify the burden of subclinical plaques, and treat to lower lipid targets using statins and newer therapies, such as PCSK9 inhibitors, that decrease ASCVD events in nonautoimmune cohorts. More clinical vigilance is needed regarding surveillance, prevention, risk modification, and treatment of dyslipidemias, hypertension, and smoking in patients with LE or DM. All of these goals are achievable.

Cutaneous lupus erythematosus (CLE) is an autoimmune disease that can occur with or without underlying systemic lupus erythematosus (SLE) and often has a profoundly negative impact on patient quality of life. There is substantial need for new and more effective therapies to treat CLE. CLE has a multifactorial pathogenesis that involves several key immune cells and pathways, including abnormalities in innate (e.g., type 1 interferon pathways) and adaptive immune responses (e.g., B and T cell autoreactivity), presenting multiple opportunities for more targeted therapies that do not require immunosuppression. Here we review several emerging therapies and their efficacy in CLE. Anifrolumab and belimumab have both been approved for the treatment of SLE in recent years, and clinical trial evidence suggests some forms of CLE may improve with these agents. Therapies currently in development that are being evaluated with CLE-specific outcome measures include BIIB059 and VIB7734, which target plasmacytoid dendritic cells (pDCs), and iberdomide, a cereblon modulator. These novel therapies all have previously demonstrated clinical benefit in some forms of CLE. Other therapies which target molecules believed to play a role in CLE pathogenesis, such as Janus kinases (JAKs), spleen tyrosine kinase (SYK), interferon γ (IFNγ), IL-12, and IL-23, have been evaluated in lupus clinical trials with skin-specific outcomes but failed to meet their primary endpoints.

An estimated 20–25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven by a complex interplay of genetics and environmental factors. Autoimmunity is another important cause of chronic skin inflammation. The autoimmune response may be mainly T cell driven, such as in alopecia areata or vitiligo, or B cell driven in chronic spontaneous urticaria, pemphigus and pemphigoid diseases. Rare causes of chronic skin inflammation are autoinflammatory diseases, or rheumatic diseases, such as cutaneous lupus erythematosus or dermatomyositis. Whilst we have seen a significant improvement in diagnosis and treatment, several challenges remain. Especially for rarer causes of chronic skin inflammation, early diagnosis is often missed because of low awareness and lack of diagnostics. Systemic immunosuppression is the treatment of choice for almost all of these diseases. Adverse events due to immunosuppression, insufficient therapeutic responses and relapses remain a challenge. For atopic dermatitis and psoriasis, a broad spectrum of innovative treatments has been developed. However, treatment responses cannot be predicted so far. Hence, development of (bio)markers allowing selection of specific medications for individual patients is needed. Given the encouraging developments during the past years, we envision that many of these challenges in the diagnosis and treatment of chronic inflammatory skin diseases will be thoroughly addressed in the future.

BackgroundVaccination against COVID-19 reduces the risk of severe COVID-19 disease and death. However, few studies have examined the safety of the COVID-19 vaccine in patients with autoimmune skin disease.ObjectivesWe sought to determine the incidence of disease exacerbation in this population following COVID-19 vaccination as well as the associated factors.MethodsWe performed a chart review of all patients seen in the autoimmune skin disease clinic of the principal investigator during the study period. All patients included for analysis were systematically and prospectively asked about COVID-19 vaccination status, manufacturers, vaccine dates, autoimmune symptoms after the vaccine, and timing of symptom onset using a standardized template as part of their visit. Demographics and autoimmune disease diagnosis were also collected. Analysis used Chi-square and Fisher’s exact tests.Results402 subjects were included for analysis. 85.6% of patients were fully vaccinated, with 12.9% unvaccinated and 1.5% partially vaccinated. 14.8% of fully vaccinated patients reported worsening autoimmune signs and symptoms after the vaccine. Fully vaccinated dermatomyositis patients were more likely to report worsening autoimmune signs and symptoms after the vaccine (22.7%) than fully vaccinated lupus erythematosus patients (8.6%) (p=0.009). Patients fully vaccinated with the Moderna vaccine trended towards an increased likelihood of reporting worsening autoimmune signs and symptoms after the vaccine (19.1%) than those with the Pfizer-BioNTech vaccine (12.0%) (p=0.076). Of the patients who had autoimmune symptoms after vaccination, 20% had symptoms after the 1st dose, 82% after the 2nd dose, and 4% after the 3rd dose with median onset (95% confidence interval) of 7 (2,14), 14 (14,21), and 18 (7,28) days later, respectively.ConclusionsMore fully vaccinated dermatomyositis patients had exacerbation of autoimmune signs and symptoms after the vaccine than fully vaccinated lupus erythematosus patients. However, given the risks of COVID-19, clinicians should still promote vaccination in most patients with autoimmune skin disease.

It is common for multiple autoimmune diseases to occur in the same patient. However, autoimmune blistering diseases (AIBD) do not commonly associate with dermatomyositis (DM). We performed a literature review and found 12 previous reports that may be attributed to misdiagnosis, underreporting, or true rarity of association. Herein, we present a case of pemphigus vulgaris and a case of mucous membrane pemphigoid associated with DM and review the related literature. AIBD-associated interstitial lung disease, genetic predisposition, potential environmental triggers of both AIBD and DM, drug-related triggers, and paraneoplastic processes are discussed. Dermatologists must be vigilant for a second autoimmune disease in patients with AIBD that may have therapeutic implications. Keywords: Dermatomyositis, interstitial lung disease, pemphigus, pemphigoid, autoimmune, blistering

Background: Lack of established criteria for sunscreen product recommendations and potentially allergenic ingredients in sunscreens pose an issue for physicians and patients with autoimmune skin conditions. Objective: We reviewed popular sunscreens for effectiveness and potential allergenicity for recommendation and use in the autoimmune skin condition population. Methods: In this cohort study, we selected sunscreens from the bestseller lists of Amazon, Target, and CVS. Of those, sunscreens with sun protection factor of 50 to 99 and 100 that met our effectiveness criteria (52 sunscreens) were analyzed for allergenic ingredients. An allergen list was developed from the North American Contact Dermatitis Group core data and stratified into low-prevalence and high-prevalence allergens. Results: The allergenicity of popular sunscreens that met our effectiveness criteria are organized in a table by number of tiered potential allergens. Although no sunscreen was allergen-free, several products contained a minimal number of low-prevalence allergens. The most common low-prevalence allergens were chemical sunscreen ingredients avobenzone, octocrylene, and oxybenzone, and the most common high-prevalence allergen was fragrance. A limitation is that not all U.S. sunscreens were analyzed. Conclusion: With the wide range of sunscreens available, physicians and patients should be aware of the effectiveness and potential allergenicity of sunscreens and make recommendations and consumption choices accordingly. Keywords: dermatology, sunscreen, photosensitivity, allergens, contact dermatitis, autoimmune skin

Pemphigus, an autoimmune blistering disease that affects the skin and mucous membranes, adversely impacts patients' quality of life (QOL). While there are various QOL measurement tools that can be used in this disease, few studies have assessed how a patient's change in disease severity can affect their QOL. This study aims to identify which disease severity index correlates best with the change in QOL. Fifty pemphigus patients completed QOL surveys with disease severity scored over two visits. QOL was assessed with the Autoimmune Bullous Disease Quality of Life (ABQOL), Dermatology Life Quality Index (DLQI), Skindex-29, and Short Form Survey 36 (SF-36). Disease severity was scored with the Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Correlations between the change in QOL scores and change in disease severity were analyzed using Spearman's coefficient (r). The change in PDAI showed a strong correlation (r = 0.60–0.79) with changes in the ABQOL, Skindex-29 symptoms (Skindex-S), and Skindex-29 functioning (Skindex-F) subscales for all patients (n = 50). For patients with mucosal disease (n = 24), the change in PDAI showed a strong correlation with changes in the ABQOL and Skindex-S subscale. For patients without mucosal disease, the change in PDAI showed a strong correlation with the Skindex-S. The change in ABSIS showed a strong correlation with Skindex-S for all patients and patients with no mucosal involvement, but showed no strong correlations for patients with mucosal involvement. The changes in PDAI always had a stronger correlation than the changes in ABSIS scores to changes in the ABQOL, DLQI, and Skindex-29 subscales, except where the PDAI and ABSIS scores were about the same for the Skindex-S subscale in patients with no mucosal involvement (r = 0.76 and r = 0.77, respectively). PDAI is superior to ABSIS in its correlation with validated QOL tools. The QOL tools that appear to be of most use in clinical trials and patient management are the Skindex-S and ABQOL.

Objective: Dermatomyositis (DM) may result from exogenous triggers, including airborne pollutants, in genetically susceptible individuals. The United States Environmental Protection Agency's 2011 National Air Toxics Assessment (NATA) models health risks associated with airborne emissions, available by ZIP code tabulation area (ZCTA). Important contributors include point (fixed), on-road, and secondary sources. The objective of this study was to investigate the geospatial distributions of DM and subtypes, classic DM (CDM) and clinically amyopathic DM (CADM), and their associations with airborne pollutants.Methods: This retrospective cohort study identified 642 adult DM patients from 336 unique ZCTAs. GeoDa v.1.10 was used to calculate global and local Moran's indices and generate local indicator of spatial autocorrelation (LISA) maps. All Moran's indices and LISA maps were permuted 999 times.Results: Univariate global Moran's indices for DM, CDM, and CADM prevalence were not significant, but LISA maps demonstrated differential local spatial clustering and outliers. CADM prevalence correlated with point sources (bivariate global Moran's index 0.071, pseudo-p = 0.018), in contrast to CDM (−0.0053, pseudo-p = 0.46). Bivariate global Moran's indices for DM, CDM, and CADM prevalence did not correlate with other airborne toxics, but bivariate LISA maps revealed local spatial clustering and outliers.Conclusion: Prevalence of CADM, but not CDM, is geospatially correlated with fixed sources of airborne emissions. This effect is small but significant and may support the hypothesis that triggering exposures influence disease phenotype. Important limitations are NATA data and ZCTA population estimates were collected from 2011 and ZCTA of residence may not have been where patients had greatest airborne pollutant exposure.

Objective: Plasmacytoid dendritic cells (pDCs) are a major source of Type-I Interferon (IFN-I), a key driver in cutaneous lupus erythematosus (CLE). Currently evaluated in Phase II clinical trial, 24F4A (BIIB059) is an antibody targeting BDCA2, an inhibitory receptor expressed on pDCs. Given that Hydroxychloroquine (HCQ), a widely-used CLE therapy, and 24F4A are both able to inhibit pDC-derived IFN-I production; this study aimed to determine whether 24F4A would show an additional inhibitory effect on pDC response after ex vivo or in vivo treatment with HCQ.Methods: The effect of 24F4A on pDC-derived IFNα was measured from peripheral blood mononuclear cells (PBMC) either from healthy donors in presence or absence of HCQ or from CLE patients clinically exposed to various levels of HCQ. TLR7, TLR7/8, and TLR9 agonists (ssRNA, R848, and CpG-A) were used for pDC stimulation.Results: PDCs were the only producers of IFNα in response to CpG-A, R848, and ssRNA stimulation in PBMC cultures. CLE patients with higher levels of blood HCQ showed lower ex vivo pDC responses to CpG-A, but not R848 or ssRNA. In contrast, 24F4A reduced the amount of IFNα produced by pDCs from CLE patients in response to all TLR agonists, irrespective of the blood HCQ level.Conclusion: Our findings reveal that clinically-relevant HCQ concentrations partially inhibit the pDC response to TLR9 and weakly affect the response to TLR7/8 stimulation. 24F4A robustly inhibits pDC responses even in the presence of HCQ, highlighting its unique potential to disrupt pDC disease relevant biology, which could provide additional therapeutic benefit for CLE patients.

To inform our ongoing efforts to develop defining features to be incorporated into a novel set of classification criteria for discoid lupus erythematosus (DLE), we conducted a literature review using the Ovid MEDLINE database. A search was performed to identify studies reporting criteria used to distinguish DLE from other cutaneous lupus erythematosus subtypes. We examined which clinical, histopathologic, and serologic features have data to support their use as effective features in distinguishing DLE from other potential disease mimickers and cutaneous lupus subsets. Through our search, we were also able to identify gaps that exist in the literature which can inform future directions for research endeavors. We found that localization of lesions, characteristic features of damage, and the absence of high titer Ro/SSA antibody seem most effective in differentiating DLE from other cutaneous lupus erythematosus subtypes. Histopathologic features and class of immunoreactant deposition appear to be less helpful. Keywords: classification, criteria, cutaneous lupus erythematosus, definition, diagnosis, discoid lupus erythematosus

The 5th Scientific Conference of the International Pemphigus and Pemphigoid Foundation (IPPF), “Pemphigus and Pemphigoid: A New Era of Clinical and Translational Science” was held in Orlando, Florida, on May 15–16, 2018. Scientific sessions covered recent, ongoing, and future clinical trials in pemphigus and bullous pemphigoid, disease activity and quality of life instruments, and the IPPF Natural History Study. Furthermore, the meeting provided an opportunity to hear firsthand from patients, investigators, and industry about their experience enrolling for clinical trials.

To inform our ongoing efforts to develop defining features to be incorporated into a novel set of classification criteria for discoid lupus erythematosus (DLE), we conducted a literature review using the Ovid MEDLINE database. A search was performed to identify studies reporting criteria used to distinguish DLE from other cutaneous lupus erythematosus subtypes. We examined which clinical, histopathologic, and serologic features have data to support their use as effective features in distinguishing DLE from other potential disease mimickers and cutaneous lupus subsets. Through our search, we were also able to identify gaps that exist in the literature which can inform future directions for research endeavors. We found that localization of lesions, characteristic features of damage, and the absence of high titer Ro/SSA antibody seem most effective in differentiating DLE from other cutaneous lupus erythematosus subtypes. Histopathologic features and class of immunoreactant deposition appear to be less helpful. Keywords: classification, criteria, cutaneous lupus erythematosus, definition, diagnosis, discoid lupus erythematosus

Currently, no standardized classification criteria exist for cutaneous lupus erythematosus. With increased interest in studying cutaneous lupus erythematosus, specifically discoid lupus erythematosus, it is our aim to apply previously adopted methods from rheumatology to dermatologic diseases to develop feasible, validated, and standardized classification criteria useful in both academic and community practice. Here we report the progress to date to define discoid lupus erythematosus using clinical, histopathologic, and serologic features by means of a Delphi method—using a series of iterative questionnaires sent to expert stakeholders. We present specific updates from the World Congress of Dermatology 2015 meeting, at which a nominal group of expert stakeholders met to discuss the results of round 1 of the Delphi process to further clarify and harmonize specific classification items for inclusion into round 2. Key words: Discoid Lupus Erythematosus, Cutaneous Lupus Erythematosus, Lupus, Connective Tissue Diseases, Delphi method, classification criteria, World Congress of Dermatology