A 14-year-old male was admitted with a three-month history of fever and eyelid erythema and edema. The clinical course was notable for progressive weight loss, livedo reticularis, and multiple lymph node enlargements. Laboratory investigations revealed negative antinuclear antibodies,significantly reduced complement levels, positive anticardiolipin antibodies, hemolytic anemia, and proteinuria. Imaging studies demonstrated pulmonary inflammation, intracranial venous sinus thrombosis, and pericardial effusion. Based on a comprehensive assessment, the patient was diagnosed with systemic lupus erythematosus (antinuclear antibodies-negative), complicated by antiphospholipid syndrome and cerebral venous sinus thrombosis. Initial management included pulse steroid therapy, intravenous immunoglobulin, immunosuppressive agents, and heparin anticoagulation, which resulted in transient clinical improvement. During hospitalization, the patient developed acute intracranial hemorrhage, necessitating emergent surgical decompression and therapeutic adjustment. Subsequently, an active pulmonary infection emerged and was treated with antimicrobial therapy alongside Pneumocystis jirovecii pneumonia prophylaxis, leading to stabilization of his condition.This case underscores several key considerations: (1) the diagnostic complexity of childhood SLE, particularly in ANA-negative cases, which requires integration of clinical and extensive immunologic profiling; (2) the importance of testing for non-criteria antiphospholipid antibodies in suspected antiphospholipid syndrome; (3) the fact that cerebral venous sinus thrombosis is a rare but severe complication in which anticoagulation must be carefully balanced against the risk of hemorrhage; and (4) the critical need for vigilant infection prevention, proactive management, and close monitoring of drug-related toxicities. A multidisciplinary approach is essential to tailor individualized treatment strategies and optimize patient outcomes.

Tissue-resident long-lived plasma cells, whose current therapies fail to effectively eliminate them, are now recognized as key factors in refractory and relapsed autoimmune diseases such as systemic lupus erythematosus (SLE). In this study, we discovered that the most commonly used cholesterol-lowering drugs in clinical practice, particularly lipophilic statins, can deplete antibody-secreting cells (ASCs) by triggering endoplasmic reticulum stress (ERS)-mediated apoptosis. Supplementation with geranylgeranyl pyrophosphate (GGPP) completely counteracted the effects of statins on ASCs. Targeting geranylgeranyltransferase type II (GGTase Ⅱ) downstream of GGPP through the use of 3-PEHPC, a chemical inhibitor of GGTase Ⅱ, replicated the destructive effects of statins on ASCs. Additionally, by generating mice with B-cell-specific deletion of Rabggta, which encodes RABGGTA, the specific subunit of GGTase II, we further demonstrated that GGTase II is critical for antibody responses, as well as for the generation of germinal centers, memory B cells, and bone marrow plasma cells. Mechanistically, GGTase II is essential for B-cell activation and proliferation and for protecting B cells from cell death triggered by mitogenic signals. Furthermore, GGTase Ⅱ deficiency in B cells impeded disease progression in lupus-like mice. Both 3-PEHPC and atorvastatin were effective at alleviating disease activity in these lupus-like models, resulting in significant depletion of ASCs. In conclusion, our study highlights GGTase II as a potential therapeutic target for autoimmune diseases and highlights the promising role of statins in their treatment.

Population-level evidence on postoperative outcomes in systemic lupus erythematosus (SLE) remains limited. To compare postoperative outcomes between patients with SLE and matched controls and identify factors associated with complications and algorithm-defined disease reactivation. We conducted a nationwide retrospective matched cohort study using DATASUS data. Patients with SLE were matched 1:5 to controls by sex, age group, geographic macro-region, preoperative surgical risk, and surgical category. Postoperative outcomes were assessed over 180 days. Multivariable analyses assessed factors associated with outcomes within the SLE cohort. Sensitivity analyses comprised restriction to elective procedures and exclusion of patients classified with cutaneous lupus. The cohort included 1,708 patients with SLE and 8,540 controls. SLE was associated with increased risks of surgical (RR 2.20, 95% CI 1.91-2.54), clinical (RR 3.30, 95% CI 2.53-4.30), infectious (RR 3.66, 95% CI 2.88-4.64), and other procedure- or care-related complications (RR 11.33, 95% CI 6.19-20.76). Among patients undergoing obstetric procedures, SLE was associated with obstetric complications (RR 1.87, 95% CI 1.37-2.54). Within the SLE cohort, cardiovascular risk was independently associated with higher odds of clinical (adjusted OR 2.75, 95% CI 1.36-5.54) and other procedure- or care-related complications (adjusted OR 5.46, 95% CI 1.84-16.18). Associations between SLE and surgical, clinical, and infectious complications remained significant in both sensitivity analyses. Algorithm-defined SLE reactivation occurred in 3.3%. Patients with SLE had higher risks of several postoperative complications than matched controls. The contributions of disease activity and immunosuppressive treatment warrant further investigation.

Cardiovascular disease is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Although accelerated atherosclerosis is well recognized, SLE-related coronary vasculitis and microvascular injury remain underdiagnosed. Cardiac magnetic resonance (CMR) offers unique tissue characterization that may reveal atypical patterns of myocardial injury. We describe 2 patients with active SLE who presented with acute cardiac symptoms and elevated cardiac biomarkers. CMR demonstrated both classic inflammatory findings of lupus myopericarditis (subepicardial late gadolinium enhancement and pericardial enhancement) and vascular-appearing injury, including transmural and subendocardial late gadolinium enhancement. In 1 case, coronary vascular injury occurred in the setting of systemic infection and macrophage activating syndrome, whereas in the other, coronary angiography showed normal coronary arteries, supporting a nonatherosclerotic mechanism such as coronary vasculitis or microvascular thrombosis. Serial CMR demonstrated improvement following immunosuppressive therapy. CMR can identify mixed myocardial injury phenotypes in SLE, providing critical diagnostic and follow-up information beyond conventional imaging.

Rheumatological diseases (RDs) are characterized by autoimmune-mediated organ damage, with the lungs being an important target organ. Almost all compartments of the pulmonary system may be involved, with considerable heterogeneity in the frequency, severity, and spectrum of pulmonary manifestations. This heterogeneity may result in delayed diagnosis and treatment, leading to adverse outcomes. The objective of this study was to characterize the clinical, demographic, serological, and radiological features of pulmonary manifestations across a spectrum of rheumatic diseases. This cross-sectional study was conducted between 2016 and 2023 at a tertiary care center in New Delhi, India. Patients aged ≥18 years with a diagnosed or suspected RD and pulmonary manifestations were included. Patients who did not fulfill the American College of Rheumatology/European League against Rheumatism classification criteria for RD or the American Thoracic Society/European respiratory Society criteria for interstitial pneumonia with autoimmune features (IPAF), as well as those with chronic hypersensitivity pneumonitis or sequelae of previous pulmonary infections, were excluded. Of the 783 patients screened, 170 were diagnosed with rheumatology-associated lung disease (RALD) or IPAF. The mean age was 44.3 years, with a marked female predominance (85%). Rheumatoid arthritis (RA) and systemic sclerosis (SSc) accounted for 70% of cases, followed by IPAF, overlap syndromes, Sjögren syndrome (SjS), systemic lupus erythematosus (SLE), and idiopathic inflammatory myositis. Twenty-six patients with idiopathic interstitial pneumonia were reclassified as having IPAF, one of whom subsequently progressed to RA. Pulmonary symptoms preceded the diagnosis of RD in 13.6% of patients, occurred concurrently with the diagnosis in 17%, and developed during the course of RD in 69.4%. Antinuclear antibodies and rheumatoid factor were the most commonly detected autoantibodies, while anti-aminoacyl-tRNA synthetase antibodies were identified in 11 patients. RA demonstrated the broadest spectrum of pulmonary manifestations. Interstitial lung disease was the predominant pulmonary manifestation across all RDs except SLE. Non-specific interstitial pneumonia and usual interstitial pneumonia patterns accounted for 87% of cases. Other pulmonary manifestations included infections in RA and SLE; vascular and pleural involvement in RA, SSc, and SLE; and airway involvement in RA and SjS. Pulmonary manifestations may precede, coincide with, or develop after the onset of systemic features in RDs. Comprehensive pulmonary evaluation and collaborative care involving rheumatologists and pulmonologists may facilitate earlier diagnosis and optimize the management of RALDs.

Systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and ankylosing spondylitis (AS) are distinct immune-mediated diseases with different classification frameworks and usual treatment approaches. Coexistence of all three disorders in a single patient is rare and creates diagnostic and therapeutic challenges. We report a 40-year-old woman with longstanding SLE, SS associated with SLE, and subsequently recognized axial spondyloarthritis (axSpA)/AS. The patient fulfilled the 2019 ACR/EULAR classification criteria for SLE (total score ≥ 10), the 2016 ACR/EULAR classification criteria for primary SS (total score ≥ 4), and the 2009 ASAS classification criteria for axSpA through both the imaging and clinical arms. Conventional treatment options were limited by prior gastrointestinal bleeding with NSAIDs and concern for drug-induced lupus-like syndromes with TNF inhibitors. The patient remained stable on hydroxychloroquine 200 mg daily and was enrolled in a Phase 2 SLE clinical trial evaluating a JAK inhibitor. Treatment assignment was unknown during the blinded period; during the unblinded continuation phase, she was confirmed to be receiving upadacitinib 15 mg daily. Over a 6-month duration of confirmed upadacitinib exposure, clinical improvement in lupus- and sicca-related symptoms were observed, and follow-up MRI showed resolution of previously documented sacroiliitis. Although causality cannot be established from a single uncontrolled observation, the clinical and imaging improvement during confirmed upadacitinib exposure is hypothesis-generating and suggests that shared inflammatory pathways may warrant further investigation in selected overlap cases.

Sporotrichosis, a subcutaneous mycosis, can manifest as severe disseminated disease in immunocompromised hosts. This report describes a challenging case of extracutaneous sporotrichosis in a 28-year-old female with systemic lupus erythematosus (SLE) on immunosuppressive therapy, who also faced significant socioeconomic constraints. The patient initially presented to the emergency department with a painful right inguinal mass. Physical examination revealed a hemorrhagic lesion, and aspiration of the material was performed for culture, which returned negative. She was discharged but returned 2 months later with worsening symptoms and widespread lesions. During this second admission, a detailed history finally revealed contact with cats. The patient was readmitted for an inguinal lymph node biopsy. Histopathological analysis revealed granulomatous lymphadenitis with stellate necrosis, and the diagnosis was ultimately confirmed by culture, identifying Sporothrix schenckii complex. Treatment with itraconazole was initiated but later switched to liposomal amphotericin B due to hepatotoxicity. The patient completed a 1-year course of liposomal amphotericin B with an excellent clinical response. This case highlights the diagnostic complexity of sporotrichosis in patients with SLE, its potential for severe dissemination, and the impact of socioeconomic barriers on timely diagnosis and disease management.

CAR T-cell therapy has demonstrated the capacity to induce deep, drug-free remissions in patients with severe, refractory systemic lupus erythematosus (SLE), including those with lupus nephritis (LN). These observations challenge long-standing assumptions about the reversibility of autoimmune disease and raise a critical question: whether CAR T-cell therapy should remain a therapy of last resort or if trials could investigate use earlier in the disease course, when its disease-modifying potential may be greatest. When CAR T-cell therapy is administered late in the disease course, its true biologic effect may therefore be underestimated, and clinical nonresponse may be misattributed to lack of therapeutic activity rather than to persistent damage and fibrosis. CAR T-cell therapy is still experimental and undergoing investigation as a treatment option in autoimmune diseases. Given the potential for a durable disease-free, drug free remission, we propose investigating use of CAR T-cell therapy in early severe SLE. We highlight CAR T-cell therapy in SLE and LN with a brief discussion of risks and benefits from the evidence to date. The current positioning as a refractory/salvage therapy late in the treatment algorithm may limit its impact for patients with SLE at high risk of irreversible organ damage.

SLE may occur simultaneously with or subsequently to other autoimmune diseases; such cases are called overlap syndromes. Cases of SLE overlapping with three or more autoimmune diseases are extremely rare, and there is no unified standard or consensus for treatment. We report a clinical case of a patient with SLE, immune-mediated necrotizing myopathy, Sjögren's syndrome, and psoriasis. After treatment with a triple immunosuppressive regimen containing telitacicept, the patient achieved a satisfactory therapeutic response. As the first dual-pathway inhibitor targeting BLyS/APRIL, telitacicept demonstrated potential in the treatment of this complex overlap syndrome, suggesting a promising application prospect in patients with multiple coexisting autoimmune diseases.

Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a rare but relevant complication of long-term methotrexate (MTX) therapy that can closely mimic infection or disseminated malignancy. We report the case of a 65-year-old woman with a 10-year history of systemic lupus erythematosus (SLE) treated with MTX, who presented with progressive back pain, constitutional symptoms, pancytopenia, and extensive multiorgan disease. Fluorodeoxyglucose positron emission tomography (FDG PET) demonstrated widespread hypermetabolic lesions involving the lungs, liver, left adrenal gland, and skeleton, raising strong suspicion of disseminated metastatic malignancy. Two ultrasound-guided liver nodule biopsies were inconclusive, with no evidence of malignancy. Given the absence of histopathological confirmation and her prolonged MTX exposure, MTX-LPD was suspected, and MTX was discontinued. No oncologic treatment was initiated. Four months later, the patient had achieved complete clinical resolution of her symptoms, and follow-up imaging showed near-complete regression of the pulmonary, hepatic, adrenal, and most skeletal lesions.

Systemic lupus erythematosus (SLE) is a chronic, multisystemic, autoimmune, and inflammatory disease with complex and variable phenotypes and clinical presentations. Patients with SLE often experience low self-esteem, a fear of death, and difficulty in being understood by family and friends. One effective approach to managing and combating SLE is the use of mobile health (mHealth). This study aims to explore the role of mHealth in educating SLE patients on self-care. This systematic review, conducted in August 2024 and updated in February 2025, involved searches in PubMed, Scopus, Web of Science, and Google Scholar using the keywords "Mobile Health," "Lupus," and "Self-care." Studies published in English that utilized mHealth to educate SLE patients on self-care were deemed eligible for inclusion. Titles and abstracts were independently reviewed based on the inclusion criteria, and full-text articles were subsequently obtained and reviewed according to the eligibility requirements. A total of 10 studies that met the inclusion criteria were included in the systematic review. Four studies critically assessed the quality and functionality of existing mobile health applications and information technologies for lupus patients. Three mobile applications-Lupus Ohio, Lupie Diary, and Lupus Corner Health-were introduced in these studies. Two articles focused on self-care education at home using mHealth and electronic tools tailored to individual symptoms. Three studies explored web-based self-management, online education programs, and a virtual skills training program based on Acceptance and Commitment Therapy. The findings of this study indicate that the use of mHealth in educating lupus patients on self-care can significantly improve their quality of life. However, further research is needed to raise awareness among patients and their families. It is recommended that a comprehensive application be developed that can track all lupus symptoms and provide educational resources for patients.