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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.

Dermatomyositis is a multisystem autoimmune connective tissue disease that can manifest with proximal muscle weakness, interstitial lung disease, and characteristic skin findings such as erythema and papules over the dorsal joints of the hand, periungual changes, heliotrope rash, and pruritic erythematous inflammation of the chest, back, arms, legs, and scalp. Erythromelalgia is a clinical diagnosis characterized by swelling, erythema, and burning pain, typically of the extremities and often triggered by heat or exertion. It can be classified as primary, due to genetic mutations, or secondary, associated with myeloproliferative, vascular, musculoskeletal, or neurologic disease.1 There have been reports of biopsies of erythromelalgia having some features of connective tissue disease.2,3 There are also reports of erythromelalgia associated with systemic lupus erythematosus and rheumatoid arthritis, two autoimmune connective tissue diseases.4 Here, we present two cases of erythromelalgia associated with dermatomyositis, which, to our knowledge, has not been reported in the literature to date. Case 1 An 81-year-old woman with a history of treated breast cancer presented to the dermatology clinic for evaluation of swelling and discoloration of her bilateral hands and feet of approximately 10 years' duration associated with heat intolerance. She had been seen by numerous vascular and lymphedema specialists over the years with the ultimate conclusion that her swelling was not associated with a vascular etiology. The patient noticed improvement of her symptoms when she was exposed to air conditioning or cold water. At presentation, she also reported shortness of breath, a burning sensation on her feet and scalp, subjective proximal muscle weakness, dysphagia, and weight gain. Her physical examination was notable for periungual telangiectasias, scale, and erythema on the V of her neck area, her extensor arms, and around her eyes (Fig 1). She believed that the erythema on the V of her neck area started 30 years ago, indicating the possibility that she had had potentially undiagnosed amyopathic dermatomyositis (DM) for years before her diagnosis of erythromelalgia. The patient's basic laboratory workup and immunologic studies were unrevealing, and a myositis panel was negative. Muscle magnetic resonance imaging and electromyography were not performed because of the absence of muscle pain or objective weakness on physical examination. Two skin biopsy specimens from the upper portion of the arm and the dorsal surface of the hand showed interface dermatitis (Fig 2), consistent with a diagnosis of DM based on clinicopathologic correlation with typical features of DM (as opposed to lupus, drug reaction, viral exanthem, lichen planus, or graft versus host disease). Pulmonary function testing showed an obstructive pattern with decreased carbon monoxide diffusion in the lung (62%), and chest computed tomography (CT) showed stable interstitial lung changes. The malignancy workup (including age-appropriate screening and CT of the chest, abdomen, and pelvis) was negative. The patient has had some relief from the burning sensation on her feet from topical 5% lidocaine and petroleum jelly. Because of shared decision-making and risk-benefit analysis, the patient has not started immunosuppressive therapy for her DM, but she is being followed closely. Open in a separate window Fig 1 Patient 1. Swelling and erythema on bilateral hands and feet.

Dermatomyositis (DM) is a rare, systemic autoimmune disease that most frequently affects the skin, muscles, and lungs. The inflammatory infiltrate in the skin has not been fully characterized, and, in this study, we took a single-cell, unbiased approach using imaging mass cytometry. Substantial monocyte‒macrophage diversity was observed, with the CD14+ population correlating positively with Cutaneous Dermatomyositis Disease Area and Severity Index scores (P = 0.031). The T-cell compartment revealed CD4+ T, CD8+ T, and FOXP3+ T cells. Activated (CD69+) circulating memory T cells correlated positively with Cutaneous Dermatomyositis Disease Area and Severity Index scores (P = 0.0268). IFN-β protein was highly upregulated in the T-cell, macrophage, dendritic cell, and endothelial cell populations of DM skin. Myeloid dendritic cells expressed phosphorylated peroxisome proliferator‒activated receptor γ, phosphorylated IRF3, IL-4, and IL-31, and their quantity correlated with itch as measured in Skindex-29. Plasmacytoid dendritic cells colocalized with IFN-γ in addition to the known colocalization with IFN-β. Nuclear phosphorylated peroxisome proliferator‒activated receptor γ expression was found in the DM endothelium. Imaging mass cytometry allows us to characterize single cells in the immune cell population and identify upregulated cytokines and inflammatory pathways in DM. These findings have important implications for the development of future targeted therapies for DM.

Dermatomyositis (DM) is a rare inflammatory disorder commonly manifesting with proximal muscle weakness and characteristic skin findings. Classic findings include erythematous papules or macules over the small joints of the hand, periungual changes, pruritic/erythematous skin on areas including the scalp, chest, upper back, and other surfaces, as well as interstitial lung disease. Anasarca1 and chronic hyponatremia2 have rarely been reported in cases of DM, and have only been reported separately. Here, we present a case of dermatomyositis associated with both anasarca and hyponatremia.

BACKGROUND: Bruton tyrosine kinase (BTK) inhibition targets B-cell and other non-T-cell immune cells implicated in the pathophysiology of pemphigus, an autoimmune disease driven by anti-desmoglein autoantibodies. Rilzabrutinib is a new reversible, covalent BTK inhibitor demonstrating preclinical efficacy as monotherapy in canine pemphigus foliaceus. OBJECTIVES: To evaluate the efficacy and safety of oral rilzabrutinib in patients with pemphigus vulgaris in a multicentre, proof-of-concept, phase II trial. METHODS: Patients with Pemphigus Disease Area Index severity scores 8-45 received 12 weeks of oral rilzabrutinib 400-600 mg twice daily and 12 weeks of follow-up. Patients initially received between 0 and ≤ 0·5 mg kg-1 prednisone-equivalent corticosteroid (CS; i.e. 'low dose'), tapered after control of disease activity (CDA; no new lesions, existing lesions healing). The primary endpoints were CDA within 4 weeks on zero-to-low-dose CS and safety. RESULTS: In total, 27 patients with pemphigus vulgaris were included: nine newly diagnosed (33%) and 18 relapsing (67%); 11 had moderate disease (41%) and 16 moderate to severe (59%). The primary endpoint, CDA, was achieved in 14 patients (52%, 95% confidence interval 32-71): 11 using low-dose CS and three using no CS. Over 12 weeks of treatment, mean CS doses reduced from 20·0 to 11·8 mg per day for newly diagnosed patients and from 10·3 to 7·8 mg per day for relapsing patients. Six patients (22%) achieved complete response by week 24, including four (15%) by week 12. Treatment-related adverse events were mostly mild (grade 1 or 2); one patient experienced grade 3 cellulitis. CONCLUSIONS: Rilzabrutinib alone, or with much lower CS doses than usual, was safe, with rapid clinical activity in pemphigus vulgaris. These data suggest that BTK inhibition may be a promising treatment strategy and support further investigation of rilzabrutinib for the treatment of pemphigus.

Background Outcome measures of clinical trials in cutaneous lupus erythematosus (CLE) should reflect clinically meaningful improvement in disease activity, as measured by the Cutaneous Lupus Disease Area and Severity Index activity score (CLASI-A). Objective We aimed to define the degree of improvement in disease activity meaningful to a patient's quality of life. Methods The change in the CLASI-A in 126 patients needed to predict meaningful change in QoL, as defined by the Emotions and Symptoms subscales of the Skindex-29, was evaluated by linear regression models. Results In patients with an initial CLASI-A of ≥8, a 42.1% or ≥7-point and a 31.0% or ≥5-point decrease in CLASI-A predicts meaningful improvement in the Emotions and the Symptoms subscales, respectively. Limitations This is a retrospective study of prospectively collected data at a single site. Conclusions A CLASI-A score of ≥8 for trial entry allows for inclusion of patients with milder disease where CLASI-A improvement by ≥50% is clinically significant and meaningful.

Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is subacute cutaneous lupus erythematosus (SCLE) in which the disease onset is associated with the ingestion of an offending medication. It is estimated that approximately one-third of all SCLE cases are drug-induced.1 Idiopathic SCLE and DI-SCLE are serologically, histopathologically, and clinically identical, with both characterized by widespread erythematous annular-polycyclic or papulosquamous psoriasiform lesions.2 DI-SCLE symptoms can arise weeks to years after exposure to a number of medications, including proton-pump inhibitors (PPIs), antihypertensives, antibiotics, and anticonvulsants. A lesser-known phenomenon is a lupus-associated flare or change in lupus phenotype associated with medication initiation in a person who has already been diagnosed with systemic lupus erythematosus (SLE). Cases of patients with previous diagnoses of idiopathic SCLE in remission being exacerbated by PPIs and patients with autoimmune connective tissue diseases developing DI-SCLE after PPI use have been reported.3,4 Here, we present the cases of 3 patients with previous diagnoses of SLE without SCLE skin manifestations developing DI-SCLE after using PPIs or antihypertensives. This pattern has rarely been described in the literature to date and suggests a phenomenon of which clinicians should be aware.

Four major medical societies involved with hydroxychloroquine (HCQ) therapy concur on the need for common principles and cooperation to minimize the risk of ocular toxicity. At a daily dosage of ≤5 mg/kg/day actual body weight, the risk of retinal toxicity from HCQ is

The use of herbal supplements that promise to improve immune health has gained popularity among dermatology patients. However, there is little to no evidence that herbal supplements improve dermatological conditions. Several in vitro and in vivo studes have shown that Spirulina platensis, Aphanizomenon flos-aqua, Chlorella, Echinacea, and alfalfa activate immune cells, via certain cytokines and chemokines. Case reports suggest the association of ingesting immunostimulatory herbs and the clinical onset or flares of diseases characterized by an exaggerated immune response such as lupus erythematosus, dermatomyositis and autoimmune blistering disorders. Therefore, it is imperative to investigate the prevalence of herbal supplement use in this patient population. In addition, in vitro studies should examine the underlying mechanisms by which herbs stimulate immune pathways that are already overactive in autoimmune patients. CAPSULE SUMMARY: How does this article integrate into what was already known? Spirulina, Aphanizomenon flos-aqua, Chlorella, Echinacea and alfalfa have been shown to stimulate the immune system. The use of these herbs may be associated with the precipitation or flare of autoimmune skin diseases. How does it change practice? Patients with autoimmune diseases should be screened for supplement use and should be advised to avoid these immunostimulatory herbs.

Background Dermatomyositis (DM) is conventionally characterized by interface dermatitis (ID) on skin histopathology. A subset of DM patients have skin biopsies showing spongiotic dermatitis (SD), a histopathology more commonly seen in eczema. In this study we aimed to 1) identify the percentage of clinically diagnosed DM patients with SD skin biopsies, 2) identify cytokine and cell markers that can help determine if a SD skin biopsy is consistent with DM. Methods In this case-control study, biopsies from ten DM patients with SD (DM-SD) were compared to biopsies from ten healthy controls, ten patients with eczema, and 12 patients with DM with ID (DM-ID). Biopsies were stained by immunohistochemistry for MxA, IFN-β, CD11c, and BDCA2. One-way ANOVA with Bonferroni's multiple comparison test was used to compare protein expression between groups. Results 11 of 164 (6.7%) patients with a clinical diagnosis of DM at our tertiary care center were identified as having SD. MxA, IFN-β, CD11c, and BDCA2 protein expression is significantly higher in DM-SD compared to eczema and healthy controls. Expressions of MxA, IFN-β and BDCA2 were not significantly different between DM-SD and DM-ID. Conclusion Increased MxA, IFN-β, CD11c, and BDCA2 protein expression may aid in distinguishing between DM-SD and eczema and warrants further investigation. This article is protected by copyright. All rights reserved.

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune disease that can present with a variety of skin manifestations and have a dramatic effect on a patient's quality of life. Effective treatment options for this disease are limited, and the efficacy of these treatments is often supported by low levels of evidence. This makes the treatment of refractory disease especially challenging, as it is difficult to achieve a consensus on the appropriate progression of treatment beyond first- and second-line treatment options. The treatment of refractory CLE often involves some degree of immunosuppression, which carries some risk for patients and requires a thoughtful approach to the selection of medications. Some treatments that have proven to be effective in systemic disease may not be as effective in cutaneous disease, making it difficult to extrapolate from the available evidence on systemic lupus erythematosus (SLE). Ultimately, the increased use of objective skin measurements in SLE clinical trials is necessary to understand drug efficacy in CLE and develop new treatments for this challenging disease. Here, we provide clinical examples of the challenges involved in treating refractory CLE, examine the evidence currently available for treatment options, and provide an algorithmic approach to the treatment of refractory disease based on this evidence. Novel therapies under development for CLE are also discussed, as they may soon be part of the accepted treatment regimen for refractory CLE.

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disease of unknown origin characterized by an uncontrolled inflammatory process resulting in fibrosis of the skin, internal organs and vasculopathy. Manifestations of SSc are heterogenous and can include pulmonary, cardiac, neural, renal, muscular, cutaneous and orofacial complications. Recent scientific advances have led to a better understanding of disease etiopathogenesis and the development of a new classification system. Therapeutic management is often multidisciplinary and targeted toward the affected organs. Oral health care providers (OHCPs) should be familiar with SSc, particularly as it relates to its impact on the orofacial region and modifications to delivery of oral health care for patients with this condition.

Photosensitivity is a common symptom in the autoimmune diseases lupus erythematosus (LE) and dermatomyositis (DM). This review provides a framework for dermatologists, rheumatologists, and general practitioners to aid in recognizing and understanding photosensitivity reactions within the scope of these conditions. Photosensitivity reactions encompass not only cutaneous symptoms but also include systemic manifestations. Prevalence of photosensitivity is high in both LE and DM and tends to vary based on race and geographical location. Pathophysiology implicates the various effects of ultraviolet (UV) light on immunoreactants in the skin. Photoprotection remains the leading method of prevention of photosensitive response. Photosensitivity heavily impacts quality of life (QoL) in patients with LE and DM. By accurately recognizing these reactions, physicians can better treat these autoimmune conditions.

ObjectiveTo achieve consensus on a definition of remission in SLE (DORIS).BackgroundRemission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation.MethodsSeveral systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on.ResultsBased on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator’s Global Assessment ConclusionThe 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies.

ObjectiveThere 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.MethodsSixteen 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.ResultsResponses 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 (pConclusionsThese 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.

Objective: The Systemic Lupus International Collaborating Clinics (SLICC) 2012 systemic lupus erythematosus (SLE) classification criteria and the revised American College of Rheumatology (ACR) 1997 criteria are list based, counting each SLE manifestation equally. We derived a classification rule based on giving variable weights to the SLICC criteria and compared its performance to the revised ACR 1997, the unweighted SLICC 2012, and the newly reported European Alliance of Associations for Rheumatology (EULAR)/ACR 2019 criteria sets. Methods: The physician-rated patient scenarios used to develop the SLICC 2012 classification criteria were reemployed to devise a new weighted classification rule using multiple linear regression. The performance of the rule was evaluated on an independent set of expert-diagnosed patient scenarios and compared to the performance of the previously reported classification rules. Results: The weighted SLICC criteria and the EULAR/ACR 2019 criteria had less sensitivity but better specificity compared to the list-based revised ACR 1997 and SLICC 2012 classification criteria. There were no statistically significant differences between any pair of rules with respect to overall agreement with the physician diagnosis. Conclusion: The 2 new weighted classification rules did not perform better than the existing list-based rules in terms of overall agreement on a data set originally generated to assess the SLICC criteria. Given the added complexity of summing weights, researchers may prefer the unweighted SLICC criteria. However, the performance of a classification rule will always depend on the populations from which the cases and non-cases are derived and whether the goal is to prioritize sensitivity or specificity.

Clinical question What are the roles of antimalarial therapy prescribers and eye care specialists in regard to antimalarial dosing, screening for retinal toxic effects, and antimalarial treatment cessation? Bottom line Antimalarial prescribers should prescribe antimalarial dosages at 5 mg/kg/d or less of actual body weight. A baseline retinal examination with optical coherence tomography should be performed within 6 months of starting antimalarial therapy to rule out confounding disease. Patients at low risk for retinopathy do not require annual screening until 5 years of antimalarial use. Eye care clinicians should not stop treatment with antimalarials because of equivocal findings, as retinopathy occurs slowly, and therefore there is time for repeated testing. Antimalarial treatment cessation should be a collaborative decision that involves the patient, the prescriber, and the eye care clinician and that focuses on patient values, the severity of the underlying disease, and the estimated risk of visual loss if treatment with the drug is continued.

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

Cutaneous lupus erythematosus encompasses a spectrum of cutaneous disease with different phenotypes, and it potentially intersects with many disciplines in medicine. This review examines the epidemiology, clinical subtypes, pathology, psychology and intervention options for this disorder. It is important to understand the psychological distress that cutaneous lupus can cause and if needed actively investigate this possibility with the patient. Careful liaison between disciplines will achieve the optimum outcome.

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

BACKGROUND. Plasmacytoid DCs (pDC) produce large amounts of type I IFN (IFN-I), cytokines convincingly linked to systemic lupus erythematosus (SLE) pathogenesis. BIIB059 is a humanized mAb that binds blood DC antigen 2 (BDCA2), a pDC-specific receptor that inhibits the production of IFN-I and other inflammatory mediators when ligated. A first-in-human study was conducted to assess safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) effects of single BIIB059 doses in healthy volunteers (HV) and patients with SLE with active cutaneous disease as well as proof of biological activity and preliminary clinical response in the SLE cohort. METHODS. A randomized, double-blind, placebo-controlled clinical trial was conducted in HV (n = 54) and patients with SLE (n = 12). All subjects were monitored for adverse events. Serum BIIB059 concentrations, BDCA2 levels on pDCs, and IFN-responsive biomarkers in whole blood and skin biopsies were measured. Skin disease activity was determined using the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A). RESULTS. Single doses of BIIB059 were associated with favorable safety and PK profiles. BIIB059 administration led to BDCA2 internalization on pDCs, which correlated with circulating BIIB059 levels. BIIB059 administration in patients with SLE decreased expression of IFN response genes in blood, normalized MxA expression, reduced immune infiltrates in skin lesions, and decreased CLASI-A score. CONCLUSIONS. Single doses of BIIB059 were associated with favorable safety and PK/PD profiles and robust target engagement and biological activity, supporting further development of BIIB059 in SLE. The data suggest that targeting pDCs may be beneficial for patients with SLE, especially those with cutaneous manifestations. TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02106897","term_id":"NCT02106897"}}NCT02106897. FUNDING. Biogen Inc.

Objective Pruritus is an important symptom frequently accompanying various inflammatory skin conditions and some recent data indicated that it may be associated with autoimmune connective tissue diseases. The aim of this study was to assess the frequency and clinical presentation of itch in CLE. Methods A multinational, prospective, cross-sectional study was performed to assess the prevalence, intensity and clinical characteristic of pruritus in various subtypes of CLE. A total of 153 patients with active CLE lesions were included. Their age ranged between 17 and 82 years (mean 49.8 ± 15.4 years), and 115 patients (75.2%) were women. The disease activity and damage were assessed according to the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Pruritus severity was assessed with Numeric Rating Scale (NRS) and the 12-Item Pruritus Severity Scale. Dermatology Life Quality Index and EQ-5D questionnaire were used to measure quality of life. Results Pruritus was present in 116 (76.8%) of patients of whom half had NRS scoring equal or above 4 points indicating moderate or severe pruritus. Most commonly itch was localized on the scalp, face (excluding ears and nose) and arms (40.5%, 36.2%, 31.9%, respectively). Sensations connected with pruritus were most frequently described as burning, tingling and like ants crawling feeling, but 31.9% patients described it as “pure itch”. More than half of patients reported that pruritus was present every day, and it was most frequent during the evenings. The pruritus scoring and the CLASI activity score were significantly correlated (r = 0.42, p = 0.0001), while no correlation was found with the CLASI damage score (p = 0.16). Both the maximum and average itch intensity were correlated with systemic lupus erythematosus (SLE) activity measured with the Systemic Lupus Erythematosus Disease Activity Index. Conclusions Pruritus is a common, but frequently overlooked symptom of CLE. Its intensity correlates with the activity of CLE, but not with the skin damage. In more than a half of patients it occurs on a daily basis. The correlation between the intensity of pruritus and the activity of the skin lesions and the systemic involvement indicate that pruritus could be an individual indicator of both SLE and CLE activity.

Objectives To explore the safety and efficacy of filgotinib (FIL), a Janus kinase 1 inhibitor, and lanraplenib (LANRA), a spleen kinase inhibitor, in cutaneous lupus erythematosus (CLE). Methods This was a phase 2, randomized, double-blind, placebo-controlled, exploratory, proof-of-concept study of LANRA (30 mg), FIL (200 mg) or placebo (PBO) once daily for 12 weeks in patients with active CLE. At week 12, PBO patients were rerandomized 1:1 to receive LANRA or FIL for up to 36 additional weeks. Results Of 47 randomized patients, 45 were treated (PBO, n = 9; LANRA, n = 19; FIL, n = 17). The primary endpoint [change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score at week 12] was not met. The least squares mean CLASI-A score change from baseline was −5.5 (s.e. 2.56) with PBO, −4.5 (1.91) with LANRA and −8.7 (1.85) with FIL. Numerical differences between FIL and PBO were greater in select subgroups. A ≥5-point improvement in the CLASI-A score at week 12 was achieved by 50.0%, 56.3% and 68.8% in the PBO, LANRA and FIL arms, respectively. A numerically greater proportion of patients in the FIL arm (50%) also achieved ≥50% improvement in the CLASI-A score at week 12 (37.5% PBO, 31.3% LANRA). Most adverse events (AEs) were mild or moderate in severity. Two serious AEs were reported with LANRA and one with FIL. Conclusion The primary endpoint was not met. Select subgroups displayed a numerically greater treatment response to FIL relative to PBO. LANRA and FIL were generally well tolerated. Trial registration ClinicalTrials.gov identifier NCT03134222

Dermatomyositis (DM) is an autoimmune disease that affects the skin, lungs, and muscle. Although the pathogenesis of DM is not completely understood, several environmental triggers have been linked to DM onset or flare. This article specifically examines the effects of herbal supplements, drugs, infections, ultraviolet (UV) radiation, and environmental pollutants on the onset or exacerbation of DM. Herbal supplements such as Spirulina platensis, Aphanizomenon flos-aquae, Chlorella, Echinacea, and Alfalfa have been implicated and are frequently used in health foods. Medications such as hydroxyurea, TNF-α inhibitors, immune checkpoint inhibitors (ICI), and penicillamine, as well as certain viral infections, such as parvovirus B19, coxsackie virus, polyomavirus, Epstein-Barr virus (EBV), hepatitis, influenza, and human immunodeficiency viruses (HIV) have been associated with DM onset. Bacterial infections and vaccinations have also been linked to the development of DM. Additional environmental factors, including UV radiation and air pollutants, such as silica, biological/mineral dust, and particulate air matter from vehicle and industrial emissions, may also play a role in DM pathogenesis. Overall, there is general agreement that an autoimmune attack of the skin, muscle, and lungs in DM can be triggered by various environmental factors and warrants further investigation.

Hydroxychloroquine (HCQ) and chloroquine (CQ) are well-established medications used in treating systemic lupus erythematosus and rheumatoid arthritis, as well as skin conditions such as cutaneous lupus erythematosus. In rare cases, arrhythmias and conduction system abnormalities, as well as cardiomyopathy, have been reported in association with HCQ/CQ use. Recently, however, the corrected QT interval (QTc)-prolonging potential of these medications, and risk of torsade de pointes (TdP) in particular, have been highlighted in the setting of their experimental use for COVID-19 infection. This report was undertaken to summarize the current understanding of HCQ/CQ cardiac toxicity, describe QTc prolongation and TdP risks, and discuss areas of priority for future research. A working group of experts across rheumatology, cardiology, and dermatology performed a nonsystematic literature review and offered a consensus-based expert opinion. Current data clearly indicate that HCQ and CQ are invaluable medications in the management of rheumatic and dermatologic diseases, but they are associated with QTc prolongation by directly affecting cardiac repolarization. Prescribing clinicians should be cognizant of this small effect, especially in patients taking additional medications that prolong the QTc interval. Long-term use of HCQ/CQ may lead to a cardiomyopathy associated with arrhythmias and heart failure. Risk and benefit assessment should be considered prior to initiation of any medication, and both initial and ongoing risk-benefit assessments are important with regard to prescription of HCQ/CQ. While cardiac toxicity related to HCQ/CQ treatment of rheumatic diseases is rarely reported, it can be fatal. Awareness of the potential adverse cardiac effects of HCQ and CQ can increase the safe use of these medications. There is a clear need for additional research to allow better understanding of the cardiovascular risk and safety profile of these therapies used in the management of rheumatic and cutaneous diseases.

Dermatomyositis pathogenesis remains incompletely understood; however, recent work suggests a predominant IFN-1 response. We explored dermatomyositis pathogenesis by quantifying the inflammatory cells in the skin, comparing myeloid with plasmacytoid dendritic cell release of IFN-β, and assessing myeloid dendritic cell (mDC) contribution to hydroxychloroquine refractoriness. Immunohistochemistry was performed to assess cell-type expression in lesional skin biopsies from 12 patients with moderate-to-severe cutaneous dermatomyositis. Immunofluorescence, laser-capture microdissection, and flow cytometry were used to assess mDC release of IFN-β in lesional skin biopsies and blood of patients with dermatomyositis. Immunohistochemistry was utilized to determine whether myeloid or plasmacytoid dendritic cells were increased in hydroxychloroquine nonresponders. CD4+, CD11c+, and CD69+ cells were more populous in lesional skin of patients with dermatomyositis. mDCs colocalized with IFN-β by immunofluorescence and laser-capture microdissection revealed increased IFN-β mRNA expression by mDCs in lesional skin of patients with dermatomyositis. In blood, both mDCs and plasmacytoid dendritic cells were major producers of IFN-β in patients with dermatomyositis, whereas plasmacytoid dendritic cells predominately released IFN-β in healthy controls (P0.01). mDCs were significantly increased in the skin of hydroxychloroquine nonresponders compared with that in the skin of responders (P0.05). mDCs cells appear to play an important role in dermatomyositis pathogenesis and IFN-β production.

Cutaneous lupus erythematosus (CLE) has a profound impact on a patient’s quality of life (QoL), despite epidemiologic differences disease presentation. Disease activity, rather than damage, has a greater impact on QoL, and improvement in disease activity, defined by the Cutaneous Lupus Disease Area and Severity Index score for activity (CLASI-A), is correlated to improvement in QoL. We aimed to evaluate the differences between meaningful improvement in disease activity, experienced by Caucasian and African-American patients and disease subtypes. This study included 144 patients seen at the Hospital of the University of Pennsylvania who participated in a longitudinal research database of lupus patients. Patients with an initial CLASI-A ≥4 were included, and classified by their self-identified racial background and clinical disease subtype. Linear regression models were used to calculate change in disease activity needed to predict meaningful improvement in QoL, defined as a respective 9.38-point in the Emotions subscale of Skindex-29. Due to the limited number of patients with acute CLE, we compared meaningful improvement between patients with discoid lupus erythematosus (DLE) and patients with subacute CLE (SCLE). An improvement of disease activity by 58.6% and 52.5% is associated with a meaningful impact on the Emotions subscale of Caucasian and African-American patients, respectively. Decreasing disease activity by 52.1% and 55.2% is meaningful for patients with DLE and SCLE, respectively. Regardless of individual differences in disease activity and presentation of CLE, patients experience improvement in QoL, particularly in the emotional component, with similar meaningful changes in their disease activity.

The Dermatomyositis Delphi Criteria Project created 25 provisional clinical, laboratory and contextual classification criteria after an extensive literature search, three rounds of consensus exercises and nominal group discussions. These criteria will be subjected to a case-control validation study to create a combination of items that will define a more inclusive cohort of DM patients with skin-predominant disease for clinical research. Several measurement properties that need to be assessed prior to the conduct of a multicenter prospective validation study include the final purpose of the criteria set, population and disease characteristics of cases and controls for study entry, sources of samples, definition of criteria items, methods of item ranking and reduction, and consideration of criteria set validity against a comparator backdrop “gold standard” criteria. An expert committee Delphi and several online discussions among participants from the fields of dermatology, and adult and pediatric rheumatology have been conducted in order to address such issues. Constant evaluation of the methodologic process is vital to produce classification criteria which are valid and reliable to identify patients with DM and delineate these patients from those with mimicker diseases.

BACKGROUND: Dermatomyositis (DM) is an autoimmune disease affecting skin, skeletal muscle, and lungs. Pathogenesis is considered largely driven by interferon-beta (IFN-beta) and involves CD4+ cells and dendritic cells (DCs). (I) Quantify inflammatory cells and IFN-beta in skin; correlate with Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores. (II) Identify DC type contributing to refractoriness to hydroxychloroquine (HCQ). (III) Compare IFN-beta production by mDCs vs. pDCs in DM. METHODS: (I) DM skin biopsies evaluated for cells and cytokines using IHC from 12 patients with moderate-severe skin disease at baseline and after 12 weeks of therapy. (II) IHC performed on skin biopsies to compare myeloid DC (mDC) and pDC expression in HCQ-responders vs. -nonresponders. (III) Flow cytometry performed on PBMCs from 5 healthy controls and 5 DM patients. RESULTS: (I) CD4+ cells, macrophages, mDCs, and TRM cells were the most populous in DM skin, followed by CD8+ cells, mast cells, and pDCs. Change in CD4+ and CD8+ cells/HPF significantly correlated with change in CDASI scores (r=0.82, P

Cutaneous lupus erythematosus (CLE) can present with or without features of systemic lupus erythematosus (SLE), with estimates of the incidence of isolated skin disease almost equaling the incidence of those with systemic disease. However, despite the impact CLE has on a patient's quality of life (QoL), there has been no US Food and Drug Administration (FDA) approved treatment for the disease in the past 50 years. In addition, patients with skin predominant LE are often excluded from clinical SLE trials. In the rare trials that include patients with skin predominant LE, disease activity and progression in the skin are often difficult to evaluate using multi-organ outcome measures. The need for new therapies for CLE and the lack of focus on skin outcomes has led to the development of the Cutaneous Lupus Disease Area and Severity Index (CLASI), a validated organ-specific outcome measure that is not only responsive to change in disease activity and damage but also correlated to changes in a patient's QoL. This paper will emphasize the extensive validation studies performed in developing the CLASI, as well as the importance of clinical trials using the CLASI to address the need for improved therapies for patients with lupus skin manifestations.

BACKGROUND: Dermatomyositis (DM) is conventionally characterized by interface dermatitis (ID) on skin histopathology. A subset of patients with clinically diagnosed DM have skin biopsies showing spongiotic dermatitis (SD), a histopathology more commonly seen in eczema. Diagnosis of DM is challenging, with significant delays following initial presentation. (I) To identify the percentage of clinically diagnosed DM patients with skin biopsies showing SD, (II) to identify cytokine and cell markers that can determine if a skin biopsy showing SD is consistent with DM in a patient with clinical DM. METHODS: Biopsies from 10 DM patients with SD histopathology were compared to biopsies from 10 healthy controls, 10 patients with eczema, and 12 patients with DM with ID histopathology. Skin biopsies were stained by H&E and by immunohistochemistry for MxA, IFN-beta, CD11c (mDC), and BDCA2 (pDC). Cytokines were quantified by area and intensity. Cells were quantified per HPF. Fisher’s exact test was used to compare baseline patient characteristics. One-way ANOVA with Bonferroni’s multiple comparison test was used to compare protein expression between groups. RESULTS: Eleven of 164 (6.7%) patients with a clinical diagnosis of DM at our tertiary care center were identified as having SD. MxA, IFN-beta, CD11c (mDC), and BDCA2 (pDC) protein expression is significantly higher in DM-SD compared to eczema and healthy controls. Expression of MxA, IFN-beta and BDCA2 were not significantly different between DM-SD and DM-ID. CONCLUSIONS: Increased MxA, IFN-beta, CD11c, and BDCA2 protein expression can help distinguish between DM-SD and eczema.

Cutaneous Lupus Erythematosus (CLE) and Dermatomyositis (DM) are cutaneous autoimmune diseases that have been among the least systematically studied, due in part to the lack of validated outcome instruments in the past. More recent epidemiologic studies have elucidated the incidence and prevalence of these diseases and their subtypes. In addition, the advent of validated clinical outcome measures, including the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), has led to an objective means of measuring activity and damage of the disease. These outcome measures have established the framework for evaluating responsiveness and therapeutic efficacy in clinical trials as well as longitudinal studies to study disease course.

Objective Anti-beta 2 glycoprotein I IgA is a common isotype of anti-beta 2 glycoprotein I in SLE. Anti-beta 2 glycoprotein I was not included in the American College of Rheumatology (ACR) SLE classification criteria, but was included in the Systemic Lupus International Collaborating Clinics (SLICC) criteria. We aimed to evaluate the prevalence of anti-beta 2-glycoprotein I IgA in SLE versus other rheumatic diseases. In addition, we examined the association between anti-beta 2 glycoprotein I IgA and disease manifestations in SLE. Methods The dataset consisted of 1384 patients, 657 with a consensus physician diagnosis of SLE and 727 controls with other rheumatic diseases. Anti-beta 2 glycoprotein I isotypes were measured by ELISA. Patients with a consensus diagnosis of SLE were compared to controls with respect to presence of anti-beta 2 glycoprotein I. Among patients with SLE, we assessed the association between anti-beta 2 glycoprotein I IgA and clinical manifestations. Results The prevalence of anti-beta 2 glycoprotein I IgA was 14% in SLE patients and 7% in rheumatic disease controls (odds ratio, OR 2.3, 95% CI: 1.6, 3.3). It was more common in SLE patients who were younger patients and of African descent (p = 0.019). Eleven percent of SLE patients had anti-beta 2 glycoprotein I IgA alone (no anti-beta 2 glycoprotein I IgG or IgM). There was a significant association between anti-beta 2 glycoprotein I IgA and anti-dsDNA (p = 0.001) and the other antiphospholipid antibodies (p = 0.0004). There was no significant correlation of anti-beta 2 glycoprotein I IgA with any of the other ACR or SLICC clinical criteria for SLE. Those with anti-beta 2 glycoprotein I IgA tended to have a history of thrombosis (12% vs 6%, p = 0.071), but the difference was not statistically significant. Conclusion We found the anti-beta 2 glycoprotein I IgA isotype to be more common in patients with SLE and in particular, with African descent. It could occur alone without other isotypes.

Objectives To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening. Methods A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared with the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesized via narrative review. Results Sixty-nine studies were included in the meta-analysis. DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. PM (RR 0.49) and clinically amyopathic DM (RR 0.44) subtypes, Raynaud’s phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD −1189.96) or lactate dehydrogenase (WMD −336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. CT scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers. Conclusion Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients.

A 57-year-old African American woman presented to dermatology following a two-year history of a pruritic rash initially involving the face which later progressed to her forearms, back, ears, dorsal hands, and abdomen. Physical exam revealed erythematous papules overlying the metacarpal and interphalangeal joints, periungual telangiectasias, periorbital edema, violaceous erythema of the upper eyelids as well as areas of dyspigmentation (A). There were 1-2 mm skin-colored hyperkeratotic follicular papules on the extensor arms, upper back, and abdomen, and hyperpigmented follicular plugging on the chest (B).

Plasmacytoid dendritic cells (pDCs) not only are specialized in their capacity to secrete large amounts of type I interferon (IFN) but also serve to enable both innate and adaptive immune responses through expression of additional proinflammatory cytokines, chemokines, and costimulatory molecules. Persistent activation of pDCs has been demonstrated in a number of autoimmune diseases. To evaluate the potential benefit of depleting pDCs in autoimmunity, a monoclonal antibody targeting the pDC-specific marker immunoglobulin-like transcript 7 was generated. This antibody, known as VIB7734, which was engineered for enhanced effector function, mediated rapid and potent depletion of pDCs through antibody-dependent cellular cytotoxicity. In cynomolgus monkeys, treatment with VIB7734 reduced pDCs in blood below the lower limit of normal by day 1 after the first dose. In two phase 1 studies in patients with autoimmune diseases, VIB7734 demonstrated an acceptable safety profile, comparable to that of placebo. In individuals with cutaneous lupus, VIB7734 profoundly reduced both circulating and tissue-resident pDCs, with a 97.6% median reduction in skin pDCs at study day 85 in VIB7734-treated participants. Reductions in pDCs in the skin correlated with a decrease in local type I IFN activity as well as improvements in clinical disease activity. Biomarker analysis suggests that responsiveness to pDC depletion therapy may be greater among individuals with high baseline type I IFN activity, supporting a central role for pDCs in type I IFN production in autoimmunity and further development of VIB7734 in IFN-associated diseases.

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.