Incidence and medical costs of lupus in Spanish hospitals: a retrospective database analysis.

BACKGROUND: This study aimed to assess the comorbidity profile, use of healthcare resources and medical costs of patients with systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE) treated at the hospital level in Spain. METHODS: Admission records of patients with SLE and CLE that were registered between January 2016 and December 2020 were obtained from a Spanish hospital discharge database and analyzed in a retrospective multicenter study. RESULTS: 329 patients met the criteria; 64.44% were female and 35.56% were male, with a median age of 54.65 years. Mean Charlson comorbidity index (CCI) was 2.75 in the index admission. 31.61% of the patients suffered essential hypertension, 21.96% suffered asthma and 19.76% suffered hyperlipidemia. Mortality rate was 3.95%. The most common medical procedure was heart ultrasound (19.45%) and introduction in peripheral vein of anti-inflammatory with a percutaneous approach (17.93%). Mean admission cost was €6355.99. CONCLUSIONS: Lupus patients showed a higher incidence and prevalence in the female population, with associated cardiac diseases as the main secondary conditions.

Case series of anifrolumab for treatment of cutaneous lupus erythematosus and lupus-related mucocutaneous manifestations in patients with SLE.

OBJECTIVE: To assess the efficacy of anifrolumab, a type-1 interferon receptor subunit-1 monoclonal antibody, in treating refractory cutaneous lupus erythematosus (CLE) and lupus non-specific mucocutaneous manifestations in patients with systemic lupus erythematosus (SLE). METHODS: A case series comprising four SLE patients with refractory CLE received anifrolumab (300mg) as add-on therapy. Medical history, serological markers and images were collected. Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) was assessed at baseline and post-treatment visits. RESULTS: Patient 1: Anifrolumab effectively treated refractory chronic cutaneous lupus erythematosus with lupus panniculitis and calcinosis cutis.Patient 2: Anifrolumab demonstrated rapid improvement in generalised discoid lupus, achieving a substantial reduction in CLASI-A from 40 to 8.Patient 3: Switching from belimumab to anifrolumab led to notable improvement in photosensitivity and tumid lupus.Patient 4: Anifrolumab effectively managed refractory subacute cutaneous lupus erythematosus, resulting in remarkable cutaneous improvement and successful tapering of prednisone and mycophenolate mofetil. CONCLUSION: Anifrolumab demonstrates efficacy in treating refractory CLE subtypes and lupus non-specific mucocutaneous manifestations in SLE patients. Further studies are needed to establish response rates, optimal dosing, and long-term outcomes.

Cutaneous lupus erythematosus is associated with an increased risk of cardiac and vascular diseases: a large-scale, propensity-matched global retrospective cohort study.

BACKGROUND: Autoimmune skin diseases can expedite various systemic sequelae involving other organs. Although limited to the skin, cutaneous lupus erythematosus (CLE) was noted to be associated with thromboembolic diseases. However, small cohort sizes, partially discrepant outcomes, missing data on CLE subtypes, and incomplete risk assessment limits these findings. METHODS: The Global Collaborative Network of TriNetX provides access to medical records of more than 120 million patients worldwide. We used TriNetX to elucidate the risk for cardiac and vascular diseases after diagnosis of CLE, and its subtypes chronic discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE). We included 30,315 CLE, 27,427 DLE, and 1613 SCLE patients. We performed propensity-matched cohort studies determining the risk to develop cardiac and vascular diseases (ICD10CM:I00-99) following diagnosis of CLE, DLE, or SCLE. Patients with systemic lupus erythematosus were excluded. FINDINGS: We document that CLE and its subtype DLE but less so SCLE are associated with a higher risk for various cardiac and vascular diseases. This included predominantly thromboembolic events such as pulmonary embolism, cerebral infarction, and acute myocardial infarction, but also peripheral vascular disease and pericarditis. For example, the hazard ratio of arterial embolism and thrombosis was 1.399 (confidence interval: 1.230-1.591, p < 0.0001) following CLE diagnosis. The study is limited by retrospective data collection and reliance on ICD10-disease classification. INTERPRETATION: CLE and its major subtype DLE are associated with an increased risk for the development of a wide range of cardiac and vascular diseases. FUNDING: This research was funded by Deutsche Forschungsgemeinschaft (EXC 2167, CSSL/CS01-2022) and the Excellence-Chair Program of the State of Schleswig-Holstein.

Serum pentraxin 3 in systemic lupus erythematosus: A potential indicator of cutaneous disease activity.

BACKGROUND: Although skin manifestations are common in systemic lupus erythematosus (SLE), there is still a lack of a diagnostic marker for cutaneous involvement. Pentraxin3 (PTX3) has been studied in SLE patients; however, it has not been investigated in relation to cutaneous manifestations. OBJECTIVE: To assess the serum PTX3 level in SLE patients, and to investigate its relationship with disease activity as well as with variable skin manifestations. PATIENTS AND METHODS: Thirty-four patients with SLE (17 patients with skin manifestations and 17 without) and 30 healthy subjects were included in the study. Patients were evaluated clinically for systemic and skin manifestations of SLE. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2k) and Cutaneous Lupus Erythematosus Activity and Severity Index (CLASI) scores were calculated. Serum level of PTX3 was measured in patients and controls using ELISA. RESULTS: Higher serum PTX3 level was found in SLE patients compared to controls (p < 0.001). Patients with skin manifestations showed higher SLEDAI-2k scores and had higher PTX3 level compared to those without skin manifestations (p = 0.015 and p < 0.001, respectively). PTX3 showed higher levels in association with malar rash (p < 0.001), mucosal ulcers (p < 0.001), alopecia (p < 0.001), and purpuric eruption (p = 0.002). Moreover, PTX3 level positively correlated with CLASI scores (p < 0.001). CONCLUSION: Our results reinforce the important role of Pentraxin3 in SLE patients with skin manifestations, and it may be considered an interesting biomarker for the pattern and extent of cutaneous involvement in SLE.

Panoramic view of clinical features of lupus erythematosus: a cross-sectional multicentre study from China.

OBJECTIVE: Lupus erythematosus (LE) is a complicated disease with highly heterogeneous clinical manifestations. Previous studies have rarely included all subgroups of patients with lupus and have overlooked the importance of the cutaneous manifestations thereof. We aimed to compare the demographic and clinical differences among patients with different subtypes of lupus. METHODS: This is the first real-world study with a relatively large sample size that simultaneously includes patients with isolated cutaneous lupus erythematosus (iCLE) and SLE. All samples were obtained from the Lupus Erythematosus Multicenter Case-control Study in Chinese populations (LEMCSC) (registration number: ChiCTR2100048939). Comparative analyses between different LE subgroups were performed. RESULTS: A total of 2097 patients with lupus were included, with 1865 patients with SLE, 1648 with cutaneous lupus erythematosus (CLE), and 232 with iCLE. Among the patients with CLE, 1330 had acute cutaneous lupus erythematosus (ACLE); 160 had subacute cutaneous lupus erythematosus (SCLE); and 546 had chronic cutaneous lupus erythematosus (CCLE). The study included a relatively large number of patients with CCLE subtypes, including 311 with discoid lupus erythematosus (DLE), 262 with chilblain lupus erythematosus (CHLE) and 45 with lupus erythematosus profundus (LEP). Demographic characteristics, systemic involvement, mucocutaneous manifestations and autoantibodies were significantly different among the groups. CONCLUSIONS: CLE and iCLE are two distinct disease states, and the selection of broad or narrow CLE definitions should be emphasised in scientific reports. LE-non-specific cutaneous lesions imply more severity, while self-reported photosensitivity and LE-specific cutaneous manifestations imply milder severity. Generalised ACLE appears to be a more severe state than localised ACLE, and CHLE appears to be more severe than DLE. Anti-Sjögren's syndrome-related antigen B (SSB) antibodies have higher specific directivity than anti-Sjögren's syndrome-related antigen A (SSA) antibodies for SCLE lesions. Anti-double-stranded DNA antibodies have a higher co-occurrence with ACLE and a lower co-occurrence with SCLE and CCLE. Compared with DLE, CHLE has significantly higher positive rates of anti-SSA/Ro60 (71%) and anti-SSA/Ro52 (42.4%) antibodies, whereas LEP is associated with a higher positive rate of antinucleosome antibodies (31.1%).

Topical niacinamide (Nicotinamide) treatment for discoid lupus erythematosus (DLE): A prospective pilot study.

BACKGROUND: Cutaneous lupus erythematosus is an umbrella term for a group of autoimmune connective tissue disorders affecting the skin. Discoid lupus erythematosus (DLE) is the chronic condition and most common form of cutaneous lupus erythematosus. AIMS: Current therapies of DLE are challenging and not completely satisfactory, highly expensive, off-label, or poorly available (like antimalarials due to COVID-19 outbreaks). Nicotinamide, also called niacinamide, is a water-soluble form of vitamin B3 (niacin). Its multiple effects let us think that nicotinamide could be a therapy for lupus-associated skin lesions. METHODS: We performed a prospective randomized double-blind clinical trial on 60 subjects diagnosed with Discoid lupus erythematosus using topical Nicotinamide 2% and 4% preparations in form of cream and gel on skin and scalp lesions. Control group was included using only cream/gel base as placebo control. RESULTS: Obtained data showed that topical Nicotinamide can be used for the treatment of DLE as adjuvant to other treatment regimens with good cosmetic results and minimal side effects. Topical 4% Nicotinamide is superior to 2% preparation in response but associated with a higher incidence of irritation. CONCLUSION: Topical Nicotinamide can be used for the treatment of DLE as an adjuvant to other treatment regimens with good cosmetic results and minimal side effects. Further trials with long-term therapy, follow-up period, and bigger sample sizes are required.

Hepatitis B and C virus infection in patients with Systemic and Cutaneous Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a multifactorial etiology. The primary aim of this study was to estimate HCV and HBV infection prevalence in a cohort of SLE and Cutaneous Lupus Erythematosus (CLE). We assessed the frequency of these infections in our cohort and the possible associations with disease clinical/laboratory features and disease activity status. The prevalence of chronic HBV infection was 2.2% in the CLE group, while no HBsAg positive patients were identified in the SLE group. Conversely, the prevalence of anti-HCV positive was 2.2% in the SLE group while no anti-HCV positive patients were identified in the CLE group. We found no significant association between anti-HBc positive status and clinical manifestations or disease activity status in either group of patients. Hemodialysis resulted significantly associated with anti-HBc positivity in SLE. In the present study, we found HBsAg positivity in CLE patients but not in the Systemic form (SLE); conversely, a similar prevalence of anti-HBc antibodies in both groups was observed. A possible protective role exerted by SLE in HBV infection may be hypothesized. A higher frequency of HCV infection in SLE compared to CLE suggests a possible involvement of HCV in some SLE-related clinical and immunological features.

Concurrent Interstitial Granulomatous Dermatitis and TNF-α Antagonist-Induced Lupus Syndrome Secondary to Adalimumab for Crohn's Disease.

Tumor necrosis factor (TNF) antagonists have revolutionized management for various autoimmune and inflammatory conditions, including rheumatoid arthritis (RA), inflammatory bowel disease, hidradenitis suppurativa, psoriatic arthritis, and plaque psoriasis. However, adverse effects may necessitate switching to another biologic with a different mechanism of action. Here we report TNF-α antagonist-induced lupus syndrome (TAILS) revealed by interstitial granulomatous dermatitis (IGD), in the atypical context of Crohn's disease (CD).

IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus.

Interleukin- (IL-) 33 contributes to various inflammatory processes. IL-33/ST2 activation participates in systemic lupus erythematous via binding to the receptor of Suppression of Tumorigenicity 2 protein (ST2). However, whether IL-33/ST2 interferes with the nosogenesis of cutaneous lupus erythematosus (CLE) has not been reported so far. Herein, we proposed to disclose the impacts on IL-33/ST2 activation and Ro60 on CLE and their potential implications in the photosensitization of CLE cells. IL-33, ST2, and Ro60 in CLE patients' skin lesions were detected. Murine keratinocytes stimulated with or without IL-33 were irradiated by ultraviolet B (UVB), and the levels of Ro60 and inflammation markers were determined. Keratinocytes were cocultured with J774.2 macrophages and stimulated with IL-33 for analysis of chemostasis. The results identified that IL-33, ST2, and downstream inflammation markers were significantly upregulated in CLE lesions with Ro60 overexpression. Additionally, IL-33 treatment promoted the upregulation of Ro60 induced by UVB treatment in murine keratinocytes. Moreover, IL-33 stimulates keratinocytes to induce macrophage migration via enhancing the generation of the chemokine (C-C motif) ligands 17 and 22. Meanwhile, the silencing of ST2 or nuclear factor-kappa B (NF-κB) suppression abolished IL-33-induced upregulation of Ro60 in keratinocytes. Similarly, the inhibition of SOX17 expression was followed by downregulation of Ro60 in keratinocytes following IL-33 stimulation. In addition, UVB irradiation upregulated SOX17 in keratinocytes. Conclusively, the IL-33/ST2 axis interferes with Ro60-regulated photosensitization via activating the NF-κB- and PI3K/Akt- and SOX17-related pathways.

Late-onset cutaneous lupus erythematosus patients have distinctive clinical features and demographics versus early-onset patients.

BACKGROUND: Cutaneous lupus erythematosus (CLE) can present later in life, but frequency and risk factors of late-onset CLE patients are not well characterized. The study determined frequency of late-onset CLE and compared the demographic and disease characteristics between early-onset and late-onset CLE in a cohort of patients with CLE. OBJECTIVES: To determine the frequency and compare clinical features of early-onset and late-onset CLE. METHODS: This was a cross-sectional study of CLE patients seen in outpatient dermatology clinics at University of Texas Southwestern Medical Center (UTSW) and Parkland Health and Hospital System, Dallas, TX, from April 2009 to May 2019. The primary outcome was the age of CLE onset, stratified by early-onset (<50 years) and late-onset CLE (≥50 years). Predictor variables significantly associated with CLE onset groups were identified by univariate and multivariable logistic regression analyses. RESULTS: Of the 291 CLE patients studied, 79% were early-onset, and 21% were late-onset. Multivariable logistic regression analyses identified that Caucasian race (odds ratio (OR): 2.23, 95% Confidence Interval (CI): 1.19-4.19, p = 0.013), having a CLE subtype other than chronic (OR: 2.18, 95% CI: 1.02-4.65, p = 0.044), and drug-induced cases (OR: 4.65, 95% CI: 1.18-18.24, p = 0.028) were significantly associated with late-onset CLE. Early-onset CLE patients were more likely to have oral ulcers (OR: 3.58, 95% CI: 1.46-8.78, p = 0.005) and renal disorders (OR: 4.02, 95% CI: 1.10-14.71, p = 0.036). LIMITATIONS: This was a single center study. Age of onset was self-reported and late-onset CLE cohort has a small sample size. CONCLUSIONS: Our diverse cohort of CLE patients had about one out of five patients with CLE experiencing disease onset after 50 years old. These patients have distinct demographic and clinical presentations compared to early-onset CLE patients. Providers should remain mindful of CLE in older patients with photosensitive rashes and mild systemic symptoms.