Lesions In Systemic Lupus Erythematosus Research Articles

Tofacitinib versus thalidomide for mucocutaneous lesions of systemic lupus erythematosus: A real-world CSTAR cohort study XXVII.

Thalidomide is an effective medication for refractory mucocutaneous lesions of systemic lupus erythematosus (SLE) and can treat arthritis in some autoimmune diseases, but it has some adverse reactions. Recently, the effectiveness of tofacitinib in treating mucocutaneous lesions of SLE has been reported. We aimed to compare the efficacy and safety of tofacitinib with thalidomide in treating mucocutaneous and musculoskeletal lesions in patients with SLE. This study was a real-world cohort study based on the Chinese SLE Treatment and Research group (CSTAR) registry. SLE patients who manifested mucocutaneous and/or musculoskeletal symptoms and were prescribed tofacitinib or thalidomide were included. We retrospectively conducted comparisons between the tofacitinib and thalidomide groups regarding clinical improvements, SLE disease activity, serological indicators, glucocorticoid doses, and adverse events at the 1, 3, and 6-months time points. At 3 and 6months, the tofacitinib group exhibited a higher proportion of patients with improvement in mucocutaneous and musculoskeletal issues. Additionally, a greater percentage of patients in the tofacitinib group achieved remission or a low disease activity state (LLDAS) at these time points. No significant serological improvements were observed in either the tofacitinib or thalidomide groups. Fewer adverse events were observed in the tofacitinib group than in the thalidomide group. Tofacitinib might be superior to thalidomide in the improvement of mucocutaneous and musculoskeletal lesions in SLE, and had a good safety profile.

Impact of antiphospholipid antibodies on cardiac valve lesions in systemic lupus erythematosus: a systematic review and meta-analysis

This meta-analysis assesses antiphospholipid antibodies’ (aPLs) impact on heart valve disease in Systemic Lupus Erythematosus (SLE) patients. We searched PubMed, Embase, Cochrane, and Web of Science up to January 2024 for comparative studies of heart valve disease in aPL-positive versus aPL-negative SLE patients. Fixed-effect or random-effect models were used to synthesize data, with I2 and sensitivity analyses for heterogeneity and the trim-and-fill method for publication bias. Including 25 studies with 8089 patients, of which 919 had valvular changes, aPLs significantly increased the risk of heart valve disease (OR = 2.24, 95% CI: 1.58–3.18, p < 0.001). Lupus anticoagulant (LA) indicated the highest risk (OR = 4.90, 95% CI: 2.26–10.60, p < 0.001), anticardiolipin antibodies (aCL) doubled the risk (OR = 2.69, 95% CI: 1.47–4.93, p = 0.001), and anti-β2 glycoprotein I (aβ2GPI) showed a 70% increase (OR = 1.70, 95% CI: 1.17–2.45, p = 0.005). Valve-specific analysis indicated the mitral valve was most commonly involved (26.89%), with higher occurrences in aPL-positive patients (33.34% vs. 15.92%, p = 0.053). Aortic and tricuspid valve involvements were 13.11% vs. 5.42% (p = 0.147) and 12.03% vs. 8.52% (p = 0.039), respectively. Pulmonary valve disease was rare and similar across groups (1.01% in aPL-positive vs. 1.52% in aPL-negative). Significantly, only tricuspid valve disease showed increased risk in aPL-positive patients (OR = 2.66, 95% CI: 1.05–6.75, p = 0.039). APLs notably increase the risk of heart valve disease in SLE patients, with a pronounced effect on tricuspid valve involvement. Regular cardiac assessments for aPL-positive SLE patients are crucial for timely intervention and improved prognosis.

Oral lesions of systemic lupus erythematosus: A collaborative Latin American study.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that may affect the oral mucosa. The variable spectrum of oral lesions observed in SLE can pose challenges in diagnosis, particularly when the lesions occur in isolation. The aim of this study was to describe the oral lesions occurring in patients with SLE from Latin America. This collaborative record-based study involving 11 oral and maxillofacial pathology and medicine services across Venezuela, Argentina, Chile, Brazil, and Mexico describes the clinicopathological profile of SLE-related oral lesions. Seventy patients with SLE and oral lesions were included in the study. The majority were females (75.7%; female/male ratio: 3.1:1) and white (62.1%), with a mean age of 38.4 years (range: 11-77 years). The most common site of oral lesions was the hard/soft palate (32.0%). Clinically, oral lesions predominantly presented as ulcers (26.6%), erosions (26.6%), and white lesions (23.4%). Isolated oral lesions occurred in 65.2% of individuals, while cutaneous manifestations occurred in 80.3%. The main clinical diagnostic hypothesis in 71.4% of cases was an immune-mediated disease. Oral biopsies followed by histopathological analysis were performed in 50 cases. Oral lesions of SLE exhibit a variety of clinical and histopathological features. A key point in diagnosis is that unusual oral changes without an obvious local cause may indicate a possible systemic condition presenting with oral lesions. A multidisciplinary approach, which includes regular oral examination, is warranted to identify oral lesions and provide treatment.

Clinical variants of skin and mucous membrane lesions in systemic lupus erythematosus with juvenile onset

Skin and mucous membrane lesions are frequently seen in systemic lupus erythematosus (SLE) with the juvenile onset (juSLE), and they are extremely diverse. Skin manifestations can be the initial sign of the disease, they often respond first to adequate therapy, and recurrence or the appearance of a new type of lesions is the earliest indicator of exacerbation in many patients. In severe cases, skin lesions can lead to irreversible cosmetic defects, significantly affecting the quality of life. The article presents the clinical manifestations of various variants of skin and mucous membrane lesions in SLE with a debut in childhood and adolescence, their recognition is important for the timely diagnosis of SLE, as well as the correction of therapy for an existing disease, which improves the long-term prognosis and quality of life of patients.

Skin lesions in systemic lupus erythematosus. Part 2: clinical and histological features

Skin lesions in systemic lupus erythematosus (SLE) are not just a cosmetic defect, accompanied by a deterioration in the quality of life and psychological discomfort, but, possibly, the first sign of a systemic course of disease. Systemic involvement can develop in patients with almost any type of cutaneous lupus erythematosus (CLE), requiring the study of CLE in combination with SLE. Dermatologists are the first to face with skin manifestations of SLE, while other organs and systems affection leads the patient to a rheumatologist. It is important to understand that skin lesions do not cause irreversible organ damage, but continuity of therapeutic approaches between a dermatologist and a rheumatologist is necessary. The review presents the clinical signs, diagnostic features and histological characteristics of CLE.

Skin lesions in systemic lupus erythematosus. Part 1: classification, etiology, pathogenesis

Skin and mucous membranes lesions in systemic lupus erythematosus (SLE) significantly impair the quality of life of patients, although they are not a formidable manifestation of the disease. Skin manifestations of SLE can occur both at the onset and on the late stage of the disease. Although skin and mucous membranes lesions are clearly grouped in the latest classification criteria for SLE, verification of the diagnosis requires a multidisciplinary approach. In the etiology of SLE, environmental factors, hormonal factors, and genetic predisposition play a role. Further research will reveal differences in subtypes of cutaneous lupus erythematosus and will facilitate the development of new therapies.

The impact of anti-endothelial cell antibodies (AECAs) on the development of blood vessel damage in patients with systemic lupus erythematosus: the preliminary study.

Vascular injury represents one of the most frequent lesions in systemic lupus erythematosus (SLE). The aim of the study was to assess the influence of anti-endothelial cell antibodies (AECAs) on the development of endothelial cell (EC) activation, dysfunction and subsequent vasculitis in women with SLE. Fifty six women with SLE were divided into 2 subgroups, i.e. subjects with positive AECAs (+) and those with negative AECAs (-). The control group consisted of 25 healthy women. Clinical characteristics, routine laboratory tests and circulating markers of EC activation/dysfunction, i.e. monocyte-chemotactic protein-1 (MCP-1), soluble E- and P-selectin, vascular and intercellular adhesion molecule-1 (sVCAM-1, sICAM-1), von Willebrand factor (vWF), pentraxin 3 (the marker of vasculitis) the indicator of procoagulant activity i.e. prothrombin fragment 1 + 2 (F1 + 2) were detected using ELISA and compared between patients with AECA (+), AECA (-) and control subgroups. Serum concentrations of AECAs in AECA(+), AECA(-) and control groups were 4.58 ± 2.97, 0.92 ± 0.50 and 0.72 ± 0.28 AU/ml, respectively (p < 0.001). The study showed significant increases in EC activation markers, i.e. MCP-1, sE-selectin, sVCAM-1 and F1 + 2 in SLE AECA(+) compared to SLE AECA(-) and control groups. However, the indicator of vasculitis (PTX3) was significantly lower in SLE AECA(+). Moreover, multivariate analysis of variance showed a positive correlation between AECAs and sE-selectin and sVCAM-1 levels, but not with PTX3. AECAs were involved in the initial stages of vascular damage in SLE, i.e. in EC activation and dysfunction. However, they did not play a role in the development of vasculitis.

Association of antinuclear antibodies with toxic epidermal necrolysis – A novel manifestation

Toxic epidermal necrolysis (TEN) is a potentially life-threatening dermatologic disorder characterized by widespread erythema, necrosis, and bullous detachment of the epidermis of skin and mucous membranes, resulting in exfoliation and possible sepsis and/or morbidity/mortality. Exact diagnosis of lesions is very important in terms of therapeutic intervention as well as outcome. As cutaneous hypersensitivity reactions are known to occur with increased frequency in connective tissue disease, differentiating lesions of systemic lupus erythematosus that simulate drug-induced TEN is a challenge in the practical scenario. In this case series, we discuss about three patients aged between 24 and 67 years, who presented with vesiculobullous lesions all over the body and oral mucosal ulcerations. Each of them was initially admitted in the Critical Care Unit with a provisional diagnosis of TEN. Two of the three patients recovered well and were discharged. However, the third patient, who was the oldest and had multiple comorbidities, could not be saved and succumbed after 75 days of hospital stay.

Toxic epidermal necrolysis as a variant of severe skin lesions in systemic lupus erythematosus

Toxic epidermal necrolysis (TEN) has been long believed to be the most severe manifestation of drug allergy. However, cutaneous changes as TEN in systemic lupus erythematosus (SLE) were first described in the late 1970s. As of now, the English-language literature published reports of 30 cases of such lesions in SLE. This paper describes a clinical case of TEN as a direct manifestation of SLE; the positive experience has been first depicted in using not only intravenous immunoglobulin, but also rituximab with a good therapeutic effect in Russian clinical practice.

Aconitine: A potential novel treatment for systemic lupus erythematosus

BackgroundAconitum plants have been widely used in China for thousands of years. Recent evidences indicate that aconitine, the main active ingredient of Aconitum, has immunomodulatory properties that might be useful for treating autoimmune diseases, such as rheumatoid arthritis. In this study, we conducted a pilot study to explore the effect and mechanisms of aconitine on the treatment of systemic lupus erythematosus. MethodsA pristane-induced murine model was used. The pristane-induced mice were treated with aconitine (25, 75 μg kg−1 d−1, po) for 9 weeks. Every three weeks, proteinuria was detected to monitor the kidney damage and blood was collected to measure serum levels of autoantibodies, besides the kidney pathological examination. The major B cell activating factor and major pro-inflammatory mediators, PGE2, IL-17a and IL-6, were also detected. ResultsWe found that aconitine significantly improved the mouse health, decreased the elevated blood leukocyte counts, reduced the serum level of anti-double-stranded DNA (anti-dsDNA) antibody, greatly ameliorated renal histopathologic damage and reduced IgG deposit in glomerular. Furtherly, the levels of PGE2, IL-17a and IL-6, were found to have decreased in aconitine treated mice. ConclusionWe have demonstrated that aconitine can inhibit the progression of disease and ameliorate the pathologic lesion of systemic lupus erythematosus.

Thalidomide treatment in cutaneous lesions of systemic lupus erythematosus: a multicenter study in China

Thalidomide is effective for treating severe cutaneous lupus patients. The aim of this study was to observe the optimum effective and maintenance doses of thalidomide to maximize clinical benefit and minimize side effects for patients with cutaneous lupus in China. Sixty-nine patients with lupus rash from eight hospitals in China were enrolled and treated with different doses of thalidomide. We started the dose of thalidomide at 25mg daily and gradually increased administration dose once a week until erythema was markedly improved. The effective and maintenance doses were documented. The size of skin lesions was noted once a week. Systemic lupus erythematosus disease activity index (SLEDAI) score, levels of erythrocyte sedimentation rate (ESR), and serum TNF-α were measured before and after treatment. The remission rates were evaluated weekly until 8weeks. Sixty-eight percent of patients showed an effective dose of 50mg daily; another 13, 10, and 9% of patients had an effective dose of 100, 75, and 25mg daily, respectively. The maintenance dose was 50mg daily for 71% of the patients, and 100, 75, and 25mg daily for 9, 14, and 6% of the patients. SLEDAI score and serum ESR levels significantly decreased 4weeks after thalidomide treatment. At the end of the fourth week, the rates of complete remission, partial remission, and no response were 56% (n = 39), 41% (n = 28), and 3% (n = 2). At the eighth week, the rate of total remission rose up to 100%. The most common side effects were drowsiness and constipation. No peripheral neuropathy was observed in these patients. Thalidomide at a dose of 50mg daily may offer a better benefit to risk ratio in the treatment of Chinese cutaneous lupus patients.

Association of Anti–Acidic Ribosomal Protein P0 and Anti–Galectin 3 Antibodies With the Development of Skin Lesions in Systemic Lupus Erythematosus

The specific autoantibodies and antigens that mediate systemic lupus erythematosus (SLE)-related organ injuries remain largely unknown. This study was undertaken to investigate the antibody-mediated immune response that leads to SLE skin lesions. The study included 85 SLE patients with lupus-specific skin lesions and 31 without skin lesions. The reactivity of serum antibody with skin antigens was determined by immunoblotting using human foreskin as the substrate. Skin antigens were identified using mass spectrometry. Serum antibody was isolated by affinity purification and was injected intracutaneously into mouse skin to determine pathogenicity. Serum antibody levels were monitored by enzyme-linked immunosorbent assay. We determined that 78% of the patients with skin lesions had serum antibodies reactive with 35-kd and/or 25-kd skin antigens, which was significantly higher than the percentage of patients without skin lesions (P < 0.0001), suggesting a correlation between immune response and skin lesions. Acidic ribosomal protein P0 (RPLP0) and galectin 3 were 2 target antigens identified from 35-kd and 25-kd proteins, respectively. Purified serum anti-RPLP0 and anti-galectin 3 antibodies induced lupus-like histologic changes after intracutaneous injection. Anti-RPLP0 and anti-galectin 3 antibody levels were significantly higher in SLE patients than in healthy controls and decreased with skin recovery. Anti-galectin 3 antibody levels were not significantly higher in SLE patients than in patients with dermatomyositis or scleroderma, but strongly related to lupus cutaneous vasculitis. Additionally, levels of the 2 antibodies were positively correlated with leukopenia and C3 deficiency, and the anti-RPLP0 antibody level was also positively correlated with arthritis and SLE disease activity. Our findings indicate that the immune response mediated by serum anti-RPLP0 and anti-galectin 3 antibodies plays a key role in the pathogenesis of SLE skin lesions. These findings provide new insights into the mechanism of SLE-related organ disorders.

Anti-high mobility group box 1 (anti-HMGB1) antibodies are not related to the occurrence of cutaneous lesions in systemic lupus erythematosus

Objectives: To investigate whether serum anti-high mobility group box 1 (anti-HMGB1) antibodies are related to the development of skin lesions in systemic lupus erythematosus (SLE).Method: This study involved 21 SLE patients with skin lesions, 18 without skin lesions, and 22 healthy controls. The presence and serum levels of anti-HMGB1-IgG and -IgM were measured by western blot and enzyme-linked immunosorbent assay (ELISA), respectively. HMGB1 expression and serum antibodies deposited in the skin were visualized by immunofluorescence staining.Results: Using western blot analysis, we detected anti-HMGB1-IgG antibodies in 13 out of 21 SLE patients with skin lesions and 11 out of 18 SLE patients without skin lesions (p > 0.05). Serum levels of anti-HMGB1-IgG measured by ELISA were also comparable between the two groups of SLE patients (p > 0.05) but were higher in patients than in healthy controls (p < 0.05). Similar results were found with serum anti-HMGB1-IgM antibodies. HMGB1 accumulated under the stratum corneum in lupus cutaneous lesions without forming immune complexes with IgG or IgM, which were mainly observed along the epidermal–dermal junction. Furthermore, serum anti-HMGB1-IgM was higher in the group of patients with arthritis than in those without arthritis.Conclusions: Based on the findings of the current study, it is unlikely that anti-HMGB1 antibodies play a role in the development of SLE cutaneous lesions.

FRI0421 Immune Effects of Human Papilloma Virus (HPV) Immunization in Patients with Systemic Lupus Erythematosus (SLE)

BackgroundWomen with SLE show an increased risk for HPV infection and development of precancerous lesions. Although HPV vaccine is safe and effective in healthy females, there are limited data on...

Diverse vascular lesions in systemic lupus erythematosus and clinical implications

Vascular injury is one of the typical symptoms of systemic lupus erythematosus (SLE), and may play a key role in the choice of treatment strategy and prediction of prognosis. In this review, diverse vascular lesions in SLE and their clinical significance are discussed. The clinical features of vascular disease in SLE differ from organ to organ, and may be extreme with regard to renal vascular lesions. Vascular lesions in SLE may be of inflammatory or thrombotic origin, and immune system dysfunction is considered to be a predominant feature. Numerous lines of evidence suggest that the activation and injury of endothelial cells might play a key role in the pathogenesis. Vascular lesions in SLE are mediated by a complex interaction between the immune system and other contributing factors. Different therapies developed for vascular lesions, both immunosuppressive and nonimmunosuppressive, should be selected based on the different clinical and pathological characteristics, and our future understanding of the different mechanisms involved.

The association of anti-annexin1 antibodies with the occurrence of skin lesions in systemic lupus erythematosus

Anti-annexin1 antibodies are associated with the subtypes of cutaneous lupus and are elevated in systemic lupus erythematosus (SLE) patients. In this study, we investigated the correlation of this antibody with the incidence of SLE skin lesions. The presence of anti-annexin1-IgG and-IgM determined by Western blot was no different among healthy controls and SLE patients with and without skin lesions. Serum levels of anti-annexin1-IgG and -IgM measured by enzyme-linked immunosorbent assay were comparable between patients with and without skin lesions, whereas anti-annexin1-IgM was lower in SLE patients than in healthy controls. Annexin1 was abundantly detected in each epidermal layer in lupus lesional skin. Additionally, anti-annexin1-IgG was higher in SLE patients with arthritis and negatively correlated with white blood cells (WBC). Anti-annexin1-IgM was higher in patients with antinuclear antibody (ANA)-positive sera, and was positively related to hemoglobin and total serum IgM. Collectively, anti-annexin1 antibodies are not related to the incidence of skin lesions in SLE, and annexin1 abundantly distributes in epidermis in lesional skin.

Prognosis of patients with systemic lupus erythematosus and discoid lesions

BACKGROUND It has been observed that patients with systemic lupus erythematosus and discoid lesions have a milder systemic disease. OBJECTIVE To compare the clinical, demographic and autoantibody profile of systemic lupus erythematosus patients with and without discoid lesions. METHODSWe carried out a retrospective study involving 288 systemic lupus erythematosus patients who met at least four classification criteria of the American College of Rheumatology for systemic lupus erythematosus, comparing the clinical, serological and demographic factors between patients with and without discoid manifestations. RESULTS Of the 288 patients, 13.8% had discoid lesions. Univariate analysis found no differences in the prevalence of malar rash, photosensitivity, arthritis, serositis, leukopenia, lymphopenia and hemolytic anemia or anemia of the central nervous system (p = ns). Renal lesions were more common in those without discoid lesions (p =0.016), and hemolysis (p<0.0001) was more common in those with discoid lesions. Regarding the profile of autoantibodies, only the anti-RNP antibody was more common in those with discoid events (p =0.04). In a logistic regression study, only the renal lesions and anti-RNP maintained their associations with discoid manifestations. CONCLUSIONPatients with lesions of systemic lupus erythematosus and discoid lesions have lower prevalence of renal involvement and a greater presence of anti RNP.

Spectrum of renal lesions in systemic lupus erythematosus: Six years' experience at a tertiary health care centre in north east India.

Spectrum of renal lesions in systemic lupus erythematosus: Six years' experience at a tertiary health care centre in north east India.

Risk factors for squamous intraepithelial lesions in systemic lupus erythematosus: A prospective cohort study

We undertook a prospective cohort study to ascertain the risk factors for the development of squamous intraepithelial lesions (SIL) in patients with systemic lupus erythematosus (SLE). One hundred thirty-seven SLE patients with a normal Papanicolaou (Pap) smear at baseline were evaluated at 6-month intervals for up to 3 years. At each visit, a Pap smear, human papillomavirus (HPV) DNA test, and clinical assessment were performed. Among the 137 patients, there were 12 incident cases (8.8%) of SIL over a median followup duration of 30.7 months (interquartile range 25.5-31.7). Among the 30 patients with HPV infection detectable by DNA testing at baseline, 9 (30%) developed SIL. The independent risk factors for the incident SIL in this group of SLE patients included the use of cyclophosphamide (CYC) ever (odds ratio [OR] 5.6, 95% confidence interval [95% CI] 1.1-29.3; P=0.041) and persistent high-risk HPV infection (OR 26.9, 95% CI 3.2-222.3; P=0.002). The use of baseline HPV testing has a higher sensitivity than abnormal cytology (defined as atypical squamous cells of undetermined significance; 47.7% versus 33.3%) in predicting the development of SIL. Independent risk factors associated with the development of SIL in SLE patients included persistent high-risk HPV infection and the use of CYC. Low-risk patients who receive negative test results on both cervical cytology screening and HPV DNA testing may not need to be rescreened within 3 years.

Diagnostic algorithm for Raynaud’s phenomenon and vascular skin lesions in systemic lupus erythematosus

Skin discolorations and skin lesions due to vascular pathologies are common clinical features in systemic lupus erythematosus. A variety of clinical manifestations such as Raynaud's phenomenon, acrocyanosis, livedo patterns, erythematous or violaceous macules and papules or necrosis are triggered by heterogeneous pathophysiological mechanisms such as vasospasm, vasculitis or thromboembolism. A standardized macro- and microvascular assessment is necessary to establish the correct diagnosis. We describe and illustrate common clinical features of vascular skin manifestations in systemic lupus erythematosus and present a diagnostic algorithm.