BACKGROUND:Pediatric skin-limited discoid lupus erythematosus (DLE-only) is rare, with limited data on risk factors for progression to systemic lupus erythematosus (SLE). OBJECTIVE:To assess incidence, risk factors, and phenotype of pediatric DLE-only progression to SLE. METHODS:In this 17-site retrospective cohort of pediatric DLE, the primary outcome was time to SLE diagnosis (American College of Rheumatology classification criterion ≥4). Kaplan-Meier estimates for 1-, 2-, and 5-year progression to SLE were generated. Cox proportional hazards modeling identified baseline predictors of progression to SLE. RESULTS:The 1-year progression rate from DLE-only to SLE was 14.4% (95% CI, 9.6-18.9). Progression to SLE was most strongly associated with baseline antinuclear antibody positivity (hazard ratio, 3.71) and older age (hazard ratio, 1.11/y). Antiphospholipid antibodies and cytopenias also predicted progression to SLE in multivariable analysis. The SLE phenotype was relatively mild, with most patients meeting mucocutaneous and laboratory criteria (22/236, 9%) and a few patients in whom other end-organ diseases developed (7/236, 3%). LIMITATIONS:Retrospective design, missing data. CONCLUSION:Antinuclear antibody-positive patients with DLE-only warrant close monitoring for progression to SLE, especially within the first year. Severe end-organ disease in patients with DLE who progress to SLE is uncommon. Future studies should test whether early recognition and intervention in DLE-only slows progression to SLE.

Cutaneous lupus erythematosus (CLE) is an autoimmune skin condition associated with a considerable treatment burden and diminished quality of life. The absence of a consensus outcome measure to evaluate therapeutic response has posed a challenge to CLE drug development. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was developed in response to this need, incorporating morphological components including erythema, scale, dyspigmentation and scarring, to reflect disease activity and damage. Numerous studies have demonstrated the utility of CLASI in capturing relevant aspects of disease from clinician- and patient-based perspectives; however, no regulatory precedent for use of clinical trial data employing CLASI to evaluate treatment response in CLE exists. Thus, the Lupus Accelerating Breakthroughs Consortium commissioned a working group of members from industry, academia, the US Food and Drug Administration (FDA) and CLE patient advocates to address the potential knowledge gaps with CLASI through evidence-based research. Upon reviewing and submitting these data to the FDA, the working group reached alignment that CLASI is a suitable outcome measure for CLE clinical trials, enabling a clearer regulatory path for clinical drug development. The group recognizes the need for additional information to assess what degree of change in CLASI captures clinically meaningful improvement. In this Expert Recommendation, a working group integrating diverse perspectives presents a comprehensive overview of the clinical relevance and applicability of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the rationale for its use as an outcome measure in clinical trials, addressing a long-standing roadblock in the development of new drugs for CLE.

Cutaneous lupus erythematosus (CLE) is a photosensitive autoimmune condition that causes decreased quality of life due to alterations in physical appearance. Poor medication adherence has been linked to impaired disease outcomes and quality of life in patients with systemic lupus erythematosus (SLE), but there is a paucity of adherence studies for those with CLE. Furthermore, patients with CLE face unique challenges in medication adherence due to decreased quality of life compared to patients with isolated SLE and cost of treatments. This retrospective cohort study describes the 90-day oral medication non-adherence rate for patients with CLE at a safety-net hospital and explores risk factors associated with non-adherence. Patients were recruited from an outpatient dermatology clinic at Parkland Health. Inclusion criteria included dermatologist-diagnosed CLE, age ≥18 years, prescribed oral lupus medications, and 90+ days of continuous refill data. Exclusion criteria included external pharmacy refills and medications dispensed at a 3-month supply. Non-adherence was defined as a variable medication possession ratio < 80

ObjectiveMetabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous autoimmune diseases, such as cutaneous lupus erythematosus (CLE), is less well studied. An improved understanding of the metabolic pathways dysregulated in CLE may lead to novel treatment options, biomarkers and insights into disease pathogenesis. The objective was to compare metabolomic profiles in the skin and sera of CLE and control patients using liquid chromatography–mass spectrometry (LC-MS).MethodsThis was a cross-sectional pilot study comparing metabolomic sera and skin profiles of patients with CLE and normal controls. Patients were recruited from outpatient dermatology clinics at the University of Texas Southwestern and Parkland Health in Dallas, Texas, from January 2019 to October 2020. Skin and serum samples underwent LC-MS analysis. Disease sample metabolite levels were compared with controls, with significance levels adjusted for multiple hypothesis testing.Results17 serum samples (9 CLE, 8 control) and 11 skin samples (5 CLE, 6 control) were analysed using LC-MS, yielding 313 known unique metabolic structures from CLE samples. Patients with CLE were found to have 11 metabolites of differential abundance in the skin, but only 2 in the sera. CLE skin showed increased levels of citrulline (log2fold change (FC)=1.15, p=0.02) and uracil (log2FC=1.79, p=0.04), and downregulation of cyclic ADP ribose (cADPr) (log2FC=0.83, p=0.04), nicotinamide mononucleotide (NMN) (log2FC=0.75, p=0.016) and nicotinamide adenine dinucleotide (NAD+) (log2FC=0.86, p=0.016) versus control skin. CLE sera had increased arabinose (log2FC=1.17, p=0.02) and cystine (log2FC=1.04, p=0.03) compared with control sera.ConclusionsMetabolites associated with the NAD+pathway may be dysregulated in the skin of patients with CLE. Available treatments including nicotinamide supplementation and anti-CD38 biologics that can correct these abnormalities can be further investigated in patients with CLE.

ImportanceAutoimmune diseases such as systemic lupus erythematosus (SLE) and psoriasis have been previously associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Whether similar increased ASCVD risk is seen with cutaneous lupus erythematosus (CLE) remains unclear.ObjectiveTo evaluate the incidence and prevalence of ASCVD among those with CLE, SLE, and psoriasis compared with a disease-free control group.Design, Setting, and ParticipantsThis retrospective, matched longitudinal cohort study used data from January 2018 to December 2020 in the IBM MarketScan Commercial Claims and Encounters Database. The control population included individuals free of CLE, SLE, and psoriasis, matched 10:1 with the CLE population on age, sex, insurance type, and enrollment duration. Data were analyzed from September 2022 to April 2024.Main Outcomes and MeasuresPrevalent ASCVD was defined as coronary artery disease, prior myocardial infarction, or cerebrovascular accident. Incident ASCVD was assessed through the number of hospitalization events through the end of follow-up (up to 3 years) in each group. Multivariable logistic regression and Cox proportional hazards models were performed to compare the prevalence and incidence of ASCVD between exposure groups, adjusting for age, sex, and cardiovascular risk factors.ResultsA total of 8138 persons with CLE (median [IQR] age, 49 [40-47] years; 6618 [81%] female), 24 675 with SLE (median [IQR] age, 46 [36-54] years; 22 432 [91%] female), 192 577 persons with psoriasis (median [IQR] age, 48 [36-56] years; 106 631 [55%] female), and 81 380 control individuals (49 [40-57] years; 66 180 [81%] female) were identified. In multivariable analysis, the odds of ASCVD were higher than control for CLE (odds ratio [OR], 1.72 [95% CI, 1.45-2.02]; P < .001) and SLE (OR, 2.41 [95% CI, 2.14-2.70]; P < .001), but not psoriasis (OR, 1.03 [95% CI, 0.95-1.11]; P = .48). At median 3 years follow-up, incidence rates of ASCVD were highest for SLE (24.8 [95% CI, 23.3-26.4] per 1000 person-years), followed by CLE (15.2 [95% CI, 13.1-17.7] per 1000 person-years), psoriasis (14.0 [95% CI, 13.5-14.4] per 1000 person-years), and then controls (10.3 [95% CI, 9.77-10.94] per 1000 person-years). In multivariable Cox proportional regression modeling with the control group as a reference group, the highest risk of incident ASCVD was in those with SLE (hazard ratio [HR], 2.23 [95% CI, 2.05-2.43]; P < .001), followed by CLE (HR, 1.32 [95% CI, 1.13-1.55]; P < .001), and psoriasis (HR, 1.06 [95% CI, 0.99-1.13]; P = .09).Conclusions and RelevanceIn this retrospective matched longitudinal cohort study, CLE was associated with an increased risk for ASCVD, similar to the risk in SLE but higher than the risk in psoriasis. The role of comorbidities that augment ASCVD risk like smoking status should be further investigated. Clinicians treating patients with CLE can consider them at increased ASCVD risk and institute appropriate screening tests.

O056 / #121 Topic:AS23 - SLE-Diagnosis, Manifestations, & Outcomes ABSTRACT CONCURRENT SESSION 09: SLE THERAPY – REVISITING OLD DRUGS AND UNLOCKING HIDDEN POTENTIAL OF NEW MEDICATIONS 24-05-2025 10:40 AM - 11:40 AM Patients with features of systemic lupus erythematosus (SLE) who do not have sufficient criteria to be classified can be designated as having incomplete lupus (ILE). This is a common condition seen in clinical practice and it has further significance as a group that has high risk of progression to SLE. Identification and treatment of those at risk has the potential to reduce the severity and incidence of SLE. Based on previous studies, hydroxychloroquine (HCQ) was chosen as an intervention for a randomized, double-blind, placebo-controlled trial to determine whether the rate of accumulation of clinical and immunologic features of SLE as defined by the 2012 SLICC criteria could be reduced. ILE was defined as ANA positivity with one or 2 additional criteria from the SLICC 2012 list. Males and females 15 to 49 years of age were eligible for enrollment. After baseline evaluation including ophthalmologic exam, participants were randomized 1:1 to HCQ or placebo. Evaluations at 3-month intervals included clinical and laboratory measures as well as patient-reported outcomes (PROs). Treatment was continued for 24 months, but if SLICC criteria were satisfied sooner, patients exited the study. Ophthalmologic exams were carried out at conclusion of treatment. A total of 187 ILE patients were randomized at 7 sites in the USA. After excluding 7 patients found to have SLE criteria at baseline when pending laboratory data were completed, 180 patients were available for analysis; 92 were randomized to HCQ and 88 received placebo. The mean age was 33 years, 91.1% were female and 74.4% were White individuals. At randomization, 65.6% had 2 SLICC criteria; the remainder had 3 SLICC criteria. The most common manifestations involved skin and joints. SLE per criteria developed in 24 participants (13.3%) during the trial who were terminated early and 40 (22%) developed additional SLICC criteria. The primary outcome was the rate of acquisition of SLICC criteria analyzed via a generalized linear mixed-effects model, with an embedded ordinal logistic regression, comparing the changes over time for the 2 arms. This showed similar slopes in the 2 groups (P=0.72). The odds of progressing to a higher SLICC score relative to the previous score was 14% smaller for every 3-month increase in time for the HCQ group and 18% smaller for the placebo group, a difference which was not statistically significant (P=0.69). A key secondary outcome was time to progression to SLE. Using a Cox proportional hazards regression model, the hazard of progressing to SLE was 10% higher for the HCQ group than for placebo, which was not a statistically significant difference (P=0.81). Adverse events were similar in the 2 groups and no serious adverse events related to use of HCQ were recorded. Five individuals were excluded from entry due to abnormal ophthalmologic findings; none developed during the trial. The SMILE results do not endorse the use of HCQ to prevent accumulation of SLICC SLE criteria. However, the definition of ILE used in SMILE does include individuals who are at risk for progressive disease and may be useful in future studies of preventive therapies. Other ongoing analyses will determine whether autoantibodies, inflammatory mediators or PROs were related to progressive illness or use of HCQ.

Skin lesions in patients with systemic lupus erythematosus can be subdivided into lupus-specific (i.e., cutaneous lupus erythematosus [CLE]) and lupus-nonspecific categories. Researchers proposed three main categories of CLE (acute, subacute, and chronic), which can be distinguished based on their clinical presentations and disease courses. Acute CLE is often transient and favors sun-exposed areas, most commonly the face. Subacute CLE lesions linger longer than acute CLE and present in photoexposed sites such as the upper trunk and extremities. Medications can account for up to one-third of patients with subacute CLE. Chronic CLE contains the largest number of subtypes with multiple different manifestations such as scarring and dyspigmentation (discoid lupus erythematosus), arcuate plaques (tumid LE), and indurated subcutaneous plaques (LE panniculitis). Most CLE subtypes share similar pathologic features including scattered dyskeratotic keratinocytes, interface dermatitis, perivascular and perifollicular inflammatory infiltrates, and increased mucin deposition. Lupus-nonspecific skin lesions, which lack these previously mentioned histologic findings, are usually present in patients with SLE as well as other autoimmune diseases, such as dermatomyositis and scleroderma. Some have served as classification criteria for SLE, whereas others result in severe disease sequelae such as vasculitis and vasculopathy. Recognition of the various skin presentations that are associated with lupus can help facilitate diagnosis and hasten appropriate treatments for these patients.

BackgroundLupus erythematosus panniculitis (LEP) is a rare variant of cutaneous lupus erythematosus that typically presents as indurated nodules or plaques. Calcinosis cutis (CC) is a potential complication of this disease with limited treatment modalities and significant quality of life complications. The rate and risk factors of CC in LEP are not well understood. Thus, we conducted a retrospective cohort study on patients diagnosed with LEP.ObjectiveTo quantify the rate of CC and to identify the risk factors associated with its development in LEP.MethodsThis retrospective cohort study analyzed data from 27 LEP patients recruited in outpatient dermatology clinics at University of Texas Southwestern Medical Center and Parkland Health from January 2009 to December 2024. The primary outcome measure was CC development based on clinical diagnosis from a dermatologist, biopsy, or radiographic imaging. Data collected included demographics, smoking history, disease duration, medications, and lesion location. Predictor variables associated with CC development were analyzed either by Mann-Whitney U or Fisher's exact tests.Results10/27 (37%) LEP patients had CC during the evaluation period. LEP patients with CC had a higher rate of truncal involvement (9/10 (90%) versus 7/17 (41.2%); p = .02) and a lower rate of head & neck involvement (3/10 (30%) versus 13/17 (76.5%); p = .04) of their LEP lesions compared to those without CC.LimitationsThis study is limited by its single-center design, retrospective nature, and small sample size.ConclusionsThis cohort of LEP patients had over a third developing CC. LEP lesion location significantly differed in those who developed CC compared with those who did not. CC is a common complication of LEP that requires close monitoring by clinicians. Prospective multicenter studies are needed to confirm these findings and better understand the predictive factors for the development of CC in LEP patients.

Background Patients with cutaneous lupus erythematosus (CLE) can present with one or multiple different subtypes of CLE. There is limited understanding of the prevalence and associated risk factors for having multiple CLE subtype diagnoses. Objective This study characterized the frequency and risk factors for having multiple CLE subtypes. Methods This was a cross-sectional study of 319 patients with CLE enrolled in the University of Texas Southwestern Cutaneous Lupus Registry seen in outpatient dermatology clinics at the University of Texas Southwestern Medical Center and Parkland Health from January 1, 2009 to December 31, 2021. Demographic and clinical information was collected from each subject and compared using univariate and multivariable logistic regression analyses. Results 59 subjects (18.5%) were diagnosed with two or more CLE subtypes. Univariate analyses identified statistically significant differences in rates of systemic lupus erythematosus (SLE) diagnosis, history of positive anti-nuclear antibody, arthritis, renal disorder, and serositis in patients with multiple CLE subtype diagnoses. In the multivariable analysis, SLE diagnosis was found to be statistically significant. Conclusions Our study showed that almost one out of five CLE patients have multiple CLE subtypes, with SLE diagnosis being a significant risk factor. Clinicians can monitor CLE patients for developing multiple subtypes and account for systemic manifestations and laboratory abnormalities associated with SLE.

PV061 / #136 Poster Topic:AS07 - Cutaneous Lupus Lupus erythematosus panniculitis (LEP) is a rare form of chronic cutaneous lupus erythematosus characterized by indurated nodules or plaques resulting in pronounced skin atrophy. Calcinosis cutis (CC) is a disease sequela associated with LEP, leading to the significant impact on patients’ quality of life due to pain and limited treatment options. The frequency of development and risk factors associated with CC in LEP remain unclear. This study aims to assess the rate of CC in LEP patients and identify factors that may increase development of CC, thereby providing insights into monitoring and management strategies for LEP patients. This retrospective cohort study reviewed data from 26 patients diagnosed with LEP and treated at the outpatient dermatology clinics of the University of Texas Southwestern Medical Center and Parkland Health between April 2009 and August 2024. The primary outcome measure was the presence of CC, confirmed through clinical evaluation by a dermatologist, biopsy, or imaging. Patient data included demographic details, smoking history, disease duration, lesion location, medications, and ANA positivity. Frequency counts and medians were calculated for categorical and continuous variables, respectively. We analyzed predictor variables for presence of CC using Mann-Whitney U and Fisher’s exact tests to examine associations. Of the 26 LEP patients, 10 (38%) were diagnosed with CC (Table 1). For these 10 patients, the median duration after diagnosis of LEP to diagnosis of CC was 3.98 years. LEP Patients that were diagnosed with calcinosis cutis had greater LEP involvement of their trunk, with 9/10 (90%) patients with LEP truncal involvement having CC, compared to only 5/16 (31%) in the group that did not have CC (p=0.01) (Table 2). The CC lesions on the 10 patients that developed this sequela were found predominantly on the trunk (6) and arms (5). No significant associations were found between CC development and other variables, including demographic factors, ANA positivity, smoking history, medications, and follow-up duration (Table 1). Table 1: Univariate analysis of demographics and clinical risk factors of lupus erythematosus panniculitis (LEP) patients with and without calcinosis cutis (CC) Table 2: Body site involvement of lupus erythematosus panniculitis (LEP) lesions in LEP patients with and without calcinosis cutis (CC) In one of the larger cohorts of LEP patients studied to date, over one-third had CC, and truncal lesions, such as those in the chest and buttocks, were significantly correlated with this complication. The median disease duration from LEP diagnosis to CC diagnosis was about 4 years. The substantial occurrence of CC in LEP highlights the need for vigilant clinical monitoring of CC in LEP. This study is limited by its single-center, retrospective design, and small sample size. Further prospective studies with larger sample sizes are necessary to confirm these results and clarify the timing and mechanisms behind CC development in LEP patients.

The treatment strategy for cutaneous lupus erythematosus (CLE) depends on the extent of skin disease, the likelihood of damage, and the response to therapy. Photoprotection, topical glucocorticoids and calcineurin inhibitors, and intralesional steroids can be used in patients with mild disease. Oral antimalarials, including hydroxychloroquine, quinacrine, and chloroquine, are first-line treatments for patients with moderate or severe CLE disease. Prednisone can be provided short term to these patients for rapid relief of symptoms, but other steroid-sparing agents are preferred for long-term treatment. Patients with moderate, severe, or refractory disease can be treated with immunosuppressives, including azathioprine, methotrexate, mycophenolate mofetil, thalidomide, lenalidomide, dapsone, retinoids, dapsone, or intravenous immunoglobulin as alternative treatments for CLE. Biologicals including rituximab and belimumab may play a role in selected cases.

Implementation of Treat-to-Target (T2T) in routine clinical practice remains low in systemic lupus erythematosus (SLE). Real-world data reveal excessive use of glucocorticoids (GCs) and frequently inadequate disease control. Here, an international task force convened to develop a consensus framework for implementing T2T in routine clinical care of adult patients with SLE. This T2T task force comprised an international panel of 22 physicians involved in the care of SLE and 3 lupus patient research partners. Following a scoping review and online discussions, during which definitions and instruments available for T2T in SLE were examined, the panel developed potential framework statements for implementing T2T in SLE, which were extensively discussed before being agreed upon by Delphi consensus. Additionally, the current challenges of implementing T2T in SLE and how future research may address these issues were analyzed. The framework comprises 5 overarching principles and 11 statements. Despite the absence of formal evidence that T2T offers superiority to conventional SLE management, T2T in SLE has been recommended for over a decade. This task force offers a framework for effectively implementing T2T in SLE from a real-life perspective, informing a wide range of physicians, including those outside the limited circle of lupus specialists.

OBJECTIVE:To provide evidence-based and expert guidance for the treatment and management of non-renal systemic lupus erythematosus (SLE); treatment and management of lupus nephritis are addressed in a separate guideline. METHODS:Clinical questions for treatment and management of SLE were developed in the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were developed for each PICO question, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess evidence quality and formulate recommendations. The Voting Panel achieved a consensus of ≥70% agreement on the direction (for or against) and strength (strong or conditional) of each recommendation. RESULTS:We present recommendations and ungraded, consensus-based good practice statements for the treatment and management of SLE that are applicable to pediatric and adult patients. Recommendations emphasize uniform treatment with hydroxychloroquine, limiting duration of glucocorticoid use, and early introduction of conventional and/or biologic immunosuppressive therapies to achieve and maintain control of SLE inflammation (remission or a low level of disease activity), reduce SLE-related morbidity and mortality, and minimize medication-related toxicities. CONCLUSION:This guideline presents direction regarding treatment and management of SLE and provides a foundation for well-informed, shared clinician-patient decision-making. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each person with SLE.

Our study seeks to further characterize the impact of CLASI-A erythema and scale on patient quality of life in a larger multicentre cohort study. We found that both erythema and scale were associated with several PROMs, both at baseline and over time, most notably with patient impressions of disease progression. These findings justify the inclusion of erythema and scale in CLASI-A scoring and has important implications for future treatment directions, as no accepted measure of disease severity currently exists for cutaneous lupus erythematosus.