Search Results (44)

Background/Objectives: Mycobacterial infections and autoimmune diseases affect many worldwide, and growing evidence suggests that there is a bidirectional relationship. This review examines mechanisms by which various autoimmune diseases predispose patients to mycobacterial infections, and vice versa. Methods: We conducted a PubMed/MEDLINE search using the keywords “mycobacterium” and the names of the autoimmune conditions to identify relevant papers. Results: Rheumatoid arthritis therapies, especially TNF-α inhibitors, raise tuberculosis (TB) and non-tuberculous mycobacteria (NTM) risk. Type 1 diabetes features impaired cell-mediated immunity and macrophage dysfunction, with evidence for Mycobacterium avium subspecies paratuberculosis (MAP) mimicry involving HSP65–GAD65. In systemic lupus erythematosus, immune dysregulation plus corticosteroids and cytotoxins elevates TB and NTM risk, amplified in endemic settings. In multiple sclerosis, heightened TLR2/4/9 signaling agents that inhibit pyrimidine synthesis may increase IL-10 and reduce antimycobacterial immunity. Crohn’s disease shows genetic susceptibility (e.g., NOD2 variants) and MAP detection, supporting impaired clearance of intracellular mycobacteria. Conclusions: Overall, evidence supports a bidirectional relationship: mycobacterial antigens can initiate or amplify autoimmunity via molecular mimicry and chronic stimulation, while autoimmune biology and iatrogenic immunosuppression increase susceptibility to infection. Implications include latent TB screening before immunosuppression, attention to local epidemiology, and vigilance for NTM. Research priorities include prospective cohorts, mechanistic studies of mimicry and NOD2–TLR pathways, safety registries, and trials of screening and prophylaxis. Full article

Background: Anti-double-stranded DNA (anti-dsDNA) antibodies are a key serological marker for systemic lupus erythematosus (SLE) and are commonly assessed in conjunction with anti-nuclear antibody (ANA) testing by indirect immunofluorescence (IIF) on HEp-2 cells. However, their detection is influenced both by the heterogeneity of the autoimmune response and by the characteristics of the analytical method employed, thereby complicating diagnostic interpretation. Methods: In this retrospective single-center study, 3090 consecutive patients undergoing anti-dsDNA analysis were screened, and 138 positive individuals, with anti-dsDNA levels ≥ 15 IU/mL by fluoroenzyme immunoassay (FEIA), were included in the study. A control group of 29 anti-dsDNA-negative patients was also analyzed. Anti-dsDNA-positive patients were stratified by antibody level (low, mild, high), and the results were correlated with HEp-2 IIF titers and fluorescence patterns. Furthermore, in a subset of 30 positive patients, anti-dsDNA antibodies were evaluated using immunoblotting (IB) and the Crithidia luciliae indirect immunofluorescence test (CLIFT). Statistical analyses assessed associations and concordance among methods. Results: Higher anti-dsDNA levels were generally associated with higher HEp-2 IIF titers. However, a considerable percentage (35%) of patients with positive anti-dsDNA were negative by HEp-2 IIF. Notably, high anti-dsDNA levels were detected in 19% of HEp-2 IIF-negative patients (titer < 1:80), 18% of mildly HEp-2 IIF-positive patients (titer 1:80–1:160), and 25% of HEp-2 IIF-positive patients (titer > 1:320). In the subset of 30 positive patients, FEIA analysis showed high concordance with the immunoblot in both IIF-positive (81%) and -negative (100%) patients, while CLIFT demonstrated lower agreement with both FEIA and IB independently of the IIF. Conclusions: Our findings indicate that anti-dsDNA antibody detection may occur independently of HEp-2 IIF positivity and that FEIA, especially when confirmed by immunoblot, represents a reliable approach for anti-dsDNA assessment. The observed results in this study likely reflect differences in epitope recognition and assay sensitivity among methods, suggesting the use of a multi-step diagnostic strategy in the serological evaluation of SLE. Full article

Background and Clinical Significance: Cutaneous lupus erythematosus (CLE) is an autoimmune condition characterized by a wide range of cutaneous manifestations, classified into three major subtypes—chronic (CCLE), subacute (SCLE), and acute (ACLE)—based on clinical morphology and lesion duration. Discoid lupus erythematosus (DLE), the most common form of CCLE, predominantly affects sun-exposed areas and presents as erythematous macules that progress to well-demarcated, disc-shaped plaques. If left untreated, DLE may lead to scarring and permanent alopecia. Diagnosis is primarily clinical, with skin biopsy performed when indicated. Management includes photoprotection and topical corticosteroids, with systemic immunosuppressive therapy reserved for severe cases. Case Presentation: We report a case of a 38-year-old female patient presenting with confluent lesions with indurated borders and multiple pustules, initially raising suspicion of cutaneous infection. A broad differential diagnosis was considered, including fungal and bacterial infections, demodicosis, and cutaneous tuberculosis, all of which were excluded through comprehensive clinical and laboratory investigations. Ultimately, DLE was diagnosed based on serologic and histopathologic findings. During the course of immunosuppressive therapy, her condition deteriorated, and she developed pulmonary tuberculosis. Conclusions: The presented case underlines the rarity and broad differential diagnosis of DLE as well as the possibility of complications. Full article

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organs and systems with a broad and heterogeneous spectrum of clinical manifestations. National disease-specific datasets and registries are crucial for clinical research since they can provide real-world and long-term data about clinical aspects, biomarkers, and treatments. Registries collect data from actual patients over time, outside the controlled environment of randomized controlled trials. This can help enhance the understanding of the natural history of a disease, provide information about how treatments work in everyday settings and elucidate potential variations in care and outcomes across different geographic areas. Here, we present a protocol for the creation of a standardized national disease-specific dataset for patients with SLE—the Systemic Lupus Erythematous Network (LUNET) Registry—which will facilitate data sharing, cross-comparison, and interoperability among centers. The LUNET registry is intended to serve as a comprehensive primary data source, capturing real-world longitudinal clinical information and the heterogeneity of patient presentations that are often underrepresented in traditional clinical trials. Ultimately, the LUNET registry will help to optimize SLE management in routine clinical practice by enabling the compilation of real-world evidence to inform clinical decision-making and health policy. Full article

Background: Youth with chronic rheumatologic diseases undergo medical experiences that can lead to post-traumatic stress disorder (PTSD). Understudied in pediatric rheumatology, medical PTSD can be significantly distressing and impairing. Objective: This study explored the prevalence of medical PTSD symptoms in youth with chronic inflammatory arthritis and associated factors, including pain, disease activity, mental health history, and anxiety sensitivity. Methods: A cross-sectional study of 50 youth (ages 8–18) with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematous (cSLE) was conducted at a pediatric rheumatology clinic. Participants completed self-report measures assessing post-traumatic stress symptoms (CPSS-V), pain, anxiety sensitivity (CASI), pain-related self-efficacy (CSES), adverse childhood experiences (ACEs), and fibromyalgia symptoms (PSAT). Clinical data included diagnoses, disease activity, treatment history, and demographics. Results: Forty percent had trauma symptoms in the moderate or more severe range. The 14% likely meeting criteria for probable medical PTSD were older (median 17 vs. 15 years, p = 0.005), had higher pain scores (median 4 vs. 3, p = 0.008), more ACEs (median 3 vs. 1, p = 0.005), higher anxiety sensitivity scores (median 39 vs. 29, p = 0.008), and higher JIA disease activity scores (median cJADAS-10 11.5 vs. 7.5, p = 0.032). They were also more likely to report a history of depression (71 vs. 23%, p = 0.020). No associations were found with hospitalization or injected/IV medication use. Conclusions: Medical trauma symptoms are prevalent in youth with chronic inflammatory arthritis. Probable PTSD was associated with pain and psychological distress. These findings support the need for trauma-informed care in pediatric rheumatology. Full article

Tinea incognito is an incorrectly diagnosed form of fungal infection due to a changed clinical picture as a result of systemic or topical corticosteroids or even local immunomodulators. This type of skin lesion is most often located on the trunk but can affect any part of the body. We present a case report of 76-year-old woman with a history of systemic lupus erythematosus who was admitted to hospital because of extensive, painful, and burning erythematous and papular lesions in an annular pattern, covered with a thick, yellow crust, located on the scalp and neck. The skin lesions were accompanied by extensive hair loss. The patient had previously undergone intensified treatment of the underlying disease due to the exacerbation of skin lesions of a subacute cutaneous lupus erythematosus type. A suspicion of tinea incognito was raised, and direct mycological examination and culture confirmed the presence of dermatophytes (Microsporum spp.). Tinea incognito can be difficult to diagnose because the clinical picture is relatively nonspecific and can mimic other dermatoses, such as subacute lupus erythematosus. Therefore, in doubtful cases it is necessary to perform a direct test and culture for fungal infection, especially before initiating treatment with glucocorticosteroids and other immunosuppressive agents. Full article

Systemic lupus erythematosus (SLE) is a pleiotropic disease that can present in numerous forms, ranging from mild mucocutaneous symptoms to severe manifestations affecting multiple organs. SLE has the potential to impact any segment of the respiratory system, exhibiting a range of severity levels throughout the different stages of the disease. Pulmonary manifestations in SLE patients can be classified as primary (i.e., directly related to SLE and to immune-mediated damage), secondary to other SLE manifestations (e.g., nephrotic syndrome, renal failure, congestive heart failure), and comorbidities (e.g., infections, cancers, overlapping primary respiratory diseases). Understanding and correctly managing lung involvement in SLE is crucial because pulmonary complications are common and can significantly impact morbidity and mortality in affected patients. Early recognition and appropriate treatment can prevent irreversible lung damage, improve quality of life, and reduce the risk of life-threatening complications. Treatment algorithms are based on the suppression of inflammation, with or without the need for dedicated, supportive care. According to disease severity, available treatments include nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants, and biological agents. In this review, we aim to summarize the current knowledge on lung involvement in SLE and then focus on the management and treatment approaches available for the different forms. Full article

Kikuchi–Fujimoto disease (KFD) is a rare condition characterized by necrotizing lymphadenitis and fever, often associated with immune dysregulation. Histologically, it features necrotic foci with abundant histiocytes and plasmacytoid dendritic cells but notably lacks neutrophils and eosinophils. Recent evidence reveals a notable prevalence among pediatric patients, who may exhibit distinct features compared to adults. We reported the case of an 11-year-old girl presenting with persistent fever, cervical adenopathy, and a malar rash, leading to a diagnosis of KFD following lymph node biopsy, which revealed non-suppurative necrosis and histiocytic infiltration. Empirical treatment with antivirals and antibiotics was ineffective, but corticosteroid therapy achieved symptom remission. A literature review identified 48 relevant studies involving 386 pediatric cases, with histopathological findings consistent with classical descriptions of KFD. Cutaneous involvement was reported in 11.14% of cases, ranging from maculopapular rashes to lupus-like eruptions. Notable complications included the development of systemic lupus erythematous, Sjögren syndrome, and rare instances of hemophagocytic syndrome or central nervous system involvement. Kikuchi–Fujimoto disease should be considered in the differential diagnosis of pediatric patients presenting with fever and lymphadenopathy, taking into account a higher frequency of cutaneous manifestations in pediatric cases. A skin biopsy may be helpful in diagnosing KFD and provide valuable information regarding the potential risk of developing systemic lupus erythematosus in the future. Full article

Senear–Usher syndrome, or pemphigus erythematosus (PE), is a rare autoimmune disorder characterized by the coexistence of features from both lupus erythematosus (LE) and pemphigus foliaceus (PF). We describe a 41-year-old patient initially diagnosed with cutaneous and then systemic lupus erythematosus (SLE), who after a few years developed new skin lesions: erythematous and erosive eruptions partially covered by crusts located on the trunk and flaccid blisters on the extremities. Direct immunofluorescence of perilesional skin revealed deposits of IgG in the intercellular space of the epidermis and granular deposits of C3 at the dermo–epidermal junction. Additional testing, revealing autoantibodies against the intercellular space of the epidermis, and direct immunofluorescence (DIF) examination allowed a diagnosis of pemphigus vulgaris coexisting with lupus. Further, DIF study revealed granular deposits of immunoglobulin G (IgG) in the intercellular spaces of the epidermis and granular deposits of the C3 along the basement membrane. Clinical appearance led to suspicion of Senear–Usher syndrome. in this patient. This case report explores the diagnostic challenges posed by the patient’s overlapping symptoms and immunological findings, suggesting an infrequent manifestation of Senear–Usher syndrome or a combination of SLE and pemphigus vulgaris. The case highlights the complexity of chronic inflammatory skin diseases and the need for tailored treatment approaches in such cases. Despite temporary improvement, the patient experienced relapses. We performed a descriptive literature review of the case reports of PE published in the last 24 years and prepared a summary of the characteristics, emphasizing the importance of proper recognition, clinical features, and treatment of this uncommon syndrome. Full article

Background/Objectives: Although hydroxychloroquine (HCQ) is used to treat systemic lupus erythematosus (SLE), it is associated with retinal toxicity. Early diagnosis can prevent the further progression of HCQ-associated retinopathy by discontinuing HCQ treatments. This study aimed to evaluate the early diagnostic parameters in patients with SLE treated with HCQ and identify the best approach using multifocal electroretinography (mfERG) and swept-source optical coherence tomography (SS-OCT) to reflect subclinical retinal toxicity. Methods: Thirty-eight patients with SLE (76 eyes) and 18 healthy controls (36 eyes) were enrolled. They were referred for HCQ retinopathy screening without visual field defects. The patients were tested using a standard 61-hexagon mfERG stimulus and SS-OCT. Ten groups of the mfERG responses from the sectors were averaged to compare the quadrants, hemiretinal areas, consecutive ring amplitudes, and ring ratios (R1/R2–R5) from the center to the periphery. Additionally, the ganglion cell complex (GCC) analyses were performed using SS-OCT. Results: No difference was observed in GCC thickness on the OCT images, in the P1 amplitudes, and in the implicit time of mfERG. However, the R1/Rx ring ratios, except the R1/R2 ratio, showed significant differences among the three groups (p = 0.759, 0.018, 0.029, and 0.029, respectively). The R1/R3, R1/R4, and R1/R5 ring ratios demonstrated a correlation with the duration of HCQ therapy (r = −0.303, −0.279, and −0.266; p = 0.003, 0.006, and 0.009). The areas under the receiver operating characteristic curve of the ring ratios R1/R3–R5 were 0.730, 0.702, and 0.724, respectively (p = 0.004, 0.012, and 0.006), indicating the likelihood of being categorized as a high-risk group for subclinical HCQ retinopathy. Conclusions: The ring ratio of mfERG reflects the subclinical electrophysiological alterations induced by HCQ and can become more clinically useful by simplifying screening examinations. Full article

Background: Systemic lupus erythematosus (SLE) is characterized by inflammation and cardiovascular complications. Our study aimed to investigate subclinical and early indicators of systolic myocardial dysfunction in SLE patients using advanced echocardiographic methods and biomarkers. Methods: In this cross-sectional study, we enrolled 102 SLE patients without known cardiac impairment and 51 healthy controls. Demographics, disease characteristics, laboratory results, disease activity (SLEDAI), and organ damage (SDI) indices were recorded. Left ventricular global longitudinal strain (GLS) and myocardial work indices were assessed by utilizing speckle tracking echocardiography. In addition, high-sensitivity C-reactive protein (hsCRP), high-sensitivity troponin (hsTn), and N-terminal-pro B-type natriuretic peptide (NT-proBNP) levels were measured in blood samples. Results: In comparison with controls, SLE patients had significantly higher GLS (−19.94 ± 2.71% vs. −21.15 ± 1.55%, p < 0.001) and global wasted work (GWW) (94 ± 71 mmHg% vs. 71 ± 49 mmHg%, p = 0.025). Notably, NT-proBNP and hsTn were threefold and twofold higher in the SLE group compared with the control group, respectively (p < 0.001). Within the SLE cohort, in patients with at least moderate disease activity (SLEDAI ≥ 4), both biomarkers were significantly more elevated than those with low disease activity (SLEDAI < 4). Notably, hsTn levels remained within the normal range. Conclusions: Advanced echocardiographic parameters combined with specific biomarkers have a promising role in detecting systolic dysfunction in SLE patients, potentially enabling timely interventions to mitigate cardiovascular risk Full article

Objective. This paper aims to estimate asymptomatic hip osteonecrosis prevalence in SLE patients using MRI examination and to determine the prevalence among higher risk subpopulations. Materials and Methods. PubMed, Embase, Cochrane, and SCOPUS were searched from inception to May 9th, 2023. Studies on patients who were clinically diagnosed with systemic lupus erythematosus without reported symptoms attributable to hip osteonecrosis were included. Two independent reviewers extracted data and assessed the risk of bias. Data collected from each study include the study year, the number of hips screened, the number of hips with osteonecrosis, demographics, laboratory data, medications, follow-up time, radiological protocols, and MRI-based osteonecrosis detection and grading criteria. Results. Eleven eligible studies including 503 participants (15–35 years old; 74–100% female) with SLE were identified. Significant risk of bias was determined in one study. The overall prevalence of osteonecrosis of the hip was found to be 14% (184/1006 hip joints, 95% confidence interval: 7–22%, number needed to scan: 7.1). SLE patients who received corticosteroid treatment had a higher prevalence of asymptomatic hip osteonecrosis (18%) compared to non-corticosteroid users (0%, p-value < 0.01). Additionally, meta-regression results revealed that daily corticosteroid dose was associated with increased prevalence of asymptomatic osteonecrosis (0.5%/milligram, p-value < 0.01). Conclusions. The high prevalence of asymptomatic hip osteonecrosis in SLE patients raises concerns about the timeliness of interventions. The limitations of this study include a relatively low number of identified studies; and one study lacked full-text availability. Full article

Despite advances in the treatment of patients with systemic lupus erythematous (SLE), outcomes have remained suboptimal. Persistent disease activity, patient comorbidities and drug toxicities contribute to the accrual of progressive irreversible damage and high rates of morbidity and mortality. Currently, similar drug doses and regimens are promulgated in the treatment guidelines for all SLE patients, despite the vast differences in patient and environmental factors that affect the drugs’ metabolism and blood concentrations. This causes a disconnect between drug dosing and drug blood concentrations, which can then result in unpredictability in drug toxicities and therapeutic effects. In this review, we discuss commonly used oral immunosuppressive medications in SLE, their pharmacogenomics, and factors affecting their metabolism and blood concentrations. Further, we highlight the role of therapeutic drug monitoring in SLE, which is the first accessible step to individualising therapy. Full article

B and T lymphocytes demonstrate important alterations in patients with systemic lupus erythematous (SLE), with a significant upregulation of double negative (DN) B cells. The aim of this study was to evaluate the correlation of T cell immunity changes with the distinct B-cell-pattern SLE. In the present study, flow cytometry was performed in 30 patients in remission of SLE and 31 healthy controls to detect DN B cells (CD19+IgD-CD27-) and a wide range of T lymphocyte subpopulations based on the presence of CD45RA, CCR7, CD31, CD28, and CD57, defined as naive, memory, and advanced differentiated/senescent T cells. Both B and T lymphocytes were significantly reduced in SLE patients. However, the percentage of DN B cells were increased compared to HC (12.9 (2.3–74.2) vs. 8 (1.7–35), p = 0.04). The distribution of CD4 and CD8 lymphocytes demonstrated a shift to advanced differentiated subsets. The population of DN B cells had a significant positive correlation with most of the early differentiated T lymphocytes, CD4CD31+, CD4CD45RA+CD28+, CD4CD45RA+CD57-, CD4CD45RA-CD57-, CD4CD28+CD57-, CD4CD28+CD57+, CD4 CM, CD8 CD31+, CD8 NAÏVE, CD8CD45RA-CD57-, CD8CD28+CD57-, and CD8CD28+CD57+. Multiple regression analysis revealed CD4CD31+, CD8CD45RA-CD57-, and CD8CD28+CD57- cells as independent parameters contributing to DN B cells, with adjusted R² = 0.534 and p < 0.0001. The predominance of DN B cells in patients with SLE is closely associated with early differentiated T lymphocyte subsets, indicating a potential causality role of DN B cells in T lymphocyte activation. Full article

Systemic lupus erythematosus (SLE) is characterized by multisystemic clinical manifestations ranging from a relatively mild involvement to potentially life-threatening complications. Due to this complexity, a multidisciplinary (MD) approach is the best strategy for optimizing patients’ care. The main aim of this systematic literature review (SLR) was to scrutinize the published data regarding the MD approach for the management of SLE patients. The secondary objective was to evaluate the outcomes of the MD approach in SLE patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used. We performed an SLR to retrieve articles available in English or Italian listed in PubMed, Embase, Cinahl, and Cochrane Library concerning the MD approach used in observational studies and clinical trials. Four independent reviewers performed the study selection and data collection. Of 5451 abstracts evaluated, 19 studies were included in the SLR. The MD approach was most frequently described in the context of SLE pregnancy, reported in 10 papers. MD teams were composed of a rheumatologist, except for one cohort study; a gynecologist; a psychologist; a nurse; and other health professionals. MD approaches had a positive impact on pregnancy-related complications and disease flares and improved SLE psychological impact. Although international recommendations advise an MD approach for managing SLE, our review highlighted the paucity of data supporting this strategy, with most of the available evidence on the management of SLE during pregnancy. Full article