Challenges and opportunities in access to care for systemic lupus erythematosus patients across Europe and worldwide.

SLE presents significant challenges for patients and health-care professionals (HCPs), both across Europe and worldwide. Improving health-care outcomes for patients with SLE requires a comprehensive understanding of patient disease pathways. In particular, the geographical distance between SLE patients and specialized care centres, combined with the scarcity of rheumatologists, exacerbates delays in diagnosis and management. Also, the initial SLE symptoms can often be non-specific, and providing guidelines for primary HCPs and other non-specialists is extremely important. Improvement in access to treatment is also important, with several recently approved therapies for SLE not being available in several European countries and many low- and middle-income countries (LMICs). Furthermore, in the LMICs in which these treatments are available, they are not always covered by the health-care system, making their access almost impossible for those of lower socio-economic status. A number of provisions are already in place within the European Union, to improve access to care for patients with rare and complex diseases, including those with SLE. In particular, European Reference Networks (ERNs), such the ERN for Autoimmune Diseases ReCONNET, are virtual networks involving HCPs across Europe with the aim of improving the care of patients with rare and complex diseases that require highly specialized treatment and a concentration of knowledge and resources. In addition, lupus patient organizations such as Lupus Europe play a crucial role in raising awareness of SLE and advocating for improved access to care. Together, we can work towards a future where all people living with lupus receive the comprehensive and timely care they deserve.

Genetic polymorphisms in genes involved in the type I interferon system (STAT4 and IRF5): association with Asian SLE patients.

Systemic lupus erythematosus (SLE) is a common autoimmune disease with a polymorphic clinical presentation involving multisystem damages with significant differences in prevalence and disease severity among different ethnic groups. Although genetic, hormonal, and environmental factors have been demonstrated to contribute a lot to SLE, the pathogenesis of SLE is still unknown. Numerous evidence revealed that gene variants within the type I interferons (IFN) signaling pathway performed the great genetic associations with autoimmune diseases including SLE. To date, through genome-wide association studies (GWAS), genetic association studies showed that more than 100 susceptibility genes have been linked to the pathogenesis of SLE, among which TYK2, STAT1, STAT4, and IRF5 are important molecules directly connected to the type I interferon signaling system. The review summarized the genetic associations and the detailed risk loci of STAT4 and IRF5 with Asian SLE patients, explored the genotype distributions associated with the main clinical manifestations of SLE, and sorted out the potential reasons for the differences in susceptibility in Asia and Europe. Moreover, the therapies targeting STAT4 and IRF5 were also evaluated in order to propose more personalized and targeted treatment plans in SLE.

Case report and literature review: management of Paxlovid (nirmatrelvir/ritonavir)-induced acute tacrolimus toxicity in a patient with systemic lupus erythematosus.

Despite the availability of effective vaccines and treatments for SARS-CoV-2, managing COVID-19 in patients with systemic lupus erythematosus (SLE) remains challenging, particularly considering drug-drug interactions (DDIs). Here, we present a case of DDIs between Tacrolimus (Tac) and nirmatrelvir/ritonavir (NMV/r) in a 32-year-old male with SLE. Following self-administration of NMV/r and resumption of Tac after 5 days, the patient experienced acute nephrotoxicity and neurotoxicity, accompanied by supratherapeutic Tac levels, despite Tac being withheld during NMV/r. The primary cause of this acute toxicity is attributed to ritonavir's inhibitory effect on both CYP3A4 enzymes and P-glycoprotein. Upon admission, Tac was discontinued, and supportive therapies were initiated. Phenytoin, a CYP3A4 inducer, was administered to lower Tac levels under the guidance of clinical pharmacists, effectively alleviating the patient's acute toxic symptoms. The half-life of Tac during the treatment of phenytoin was calculated to be 55.87 h. And no adverse reactions to phenytoin were observed. This case underscores the persistence of enzyme inhibition effects and demonstrates the effectiveness and safety of utilizing CYP3A4 enzyme inducers to mitigate Tac concentrations. Furthermore, it emphasizes the importance of healthcare providers and patients being vigilant about DDIs in Tac recipients. Lastly, it highlights the indispensable role of pharmacist involvement in clinical decision-making and close monitoring in complex clinical scenarios. Although our findings are based on a single case, they align with current knowledge and suggest the potential of individualized combination therapy in managing challenging COVID-19 cases in immunocompromised patients.

Analysis of status and influencing factors of mental health in patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder with varied clinical courses and prognoses, not only did the patients suffer from physical impairment, but also various physical and psychiatric comorbidities. Growing evidence have suggested that mental disorders in SLE patients, can lead to various adverse consequences. AIM: To explored the features and influencing factors of mental health in patients with SLE and clarifying the correlations between mental health and personality characteristics and perceived social support. The results would provide a basis for psychological intervention in patients with SLE. METHODS: The clinical data of 168 patients with SLE admitted at the First Affiliated Hospital of Hainan Medical University between June 2020 and June 2022 were collected. Psychological assessment and correlation analysis were conducted using the Symptom Checklist-90 (SCL-90) and Perceived Social Support Scale, and the collected data were compared with the national norms in China. The relevant factors influencing mental health were identified by statistical analysis. A general information questionnaire, the Revised Life Orientation Test, and Short-Form 36-Item Health Survey were employed to assess optimism level and quality of life (QoL), respectively. RESULTS: Patients with SLE obtained higher scores for the somatization, depression, anxiety, and phobic anxiety subscales than national norms (P < 0.05). A correlation was identified between total social support and total SCL-90 score or each subscale (P < 0.05). The factors significantly affecting patients' mental health were hormone dosage and disease activity index (DAI) (P < 0.05). The average optimism score of patients with SLE was 14.36 ± 4.42, and 30 cases were in the middle and lower levels. A positive correlation was found between optimism level and QoL scores. CONCLUSION: Patients with SLE develop psychological disorders at varying degrees, which are significantly influenced by hormone dosage and DAI. Patients' mental health should be closely monitored during clinical diagnosis and treatment and provided adequate support in establishing positive, healthy thinking and behavior patterns and improving their optimism level and QoL.

An Atypical Initial Presentation of Systemic Lupus Erythematous With Bilateral Lower Extremity Edema and Unilateral Pleural Effusion.

Systemic lupus erythematosus (SLE) is an autoimmune condition more commonly observed in women of childbearing age. The most commonly reported initial presentations were fatigue, arthritis, and skin manifestations. However, due to the involvement of a variety of organs, diagnosis remains a challenge for physicians. Our patient is a 48-year-old lady who presented with severe bilateral lower extremity edema with non-resolving right lower lobe pneumonia and ipsilateral exudative pleural effusion. Her leg swelling was not responding to diuretics, and her pneumonia was not improving following a course of antibiotics. This unusual presentation prompted an autoimmune workup, which later revealed a diagnosis of SLE with class 5 lupus nephritis. Pleuritis, exudative pleural effusion, and lupus nephritis have been associated with autoimmune disorders in the literature, but this is an uncommon initial presentation in SLE without other clinical manifestations. Our case report highlights the challenges in the diagnosis of an atypical case of SLE and the need to maintain high clinical suspicion for SLE, especially in female patients with multiorgan involvement.

Monoclonal antibodies targeting interleukins for systemic lupus erythematosus: updates in early clinical drug development.

INTRODUCTION: The advent of biological therapies has already revolutionized treatment strategies and disease course of several rheumatologic conditions, and monoclonal antibodies (mAbs) targeting cytokines and interleukins represent a considerable portion of this family of drugs. In systemic lupus erythematosus (SLE) dysregulation of different cytokine and interleukin-related pathways have been linked to disease development and perpetration, offering palatable therapeutic targets addressable via such mAbs. AREAS COVERED: In this review, we provide an overview of the different biological therapies under development targeting cytokines and interleukins, with a focus on mAbs, while providing the rationale behind their choice as therapeutic targets and analyzing the scientific evidence linking them to SLE pathogenesis. EXPERT OPINION: An unprecedented number of clinical trials on biological drugs targeting different immunological pathways are ongoing in SLE. Their success might allow us to tackle present challenges of SLE management, including the overuse of glucocorticoids in daily clinical practice, as well as SLE heterogenicity in treatment response among different individuals, hopefully paving the way toward precision medicine.

tRF-His-GTG-1 enhances NETs formation and interferon-α production in lupus by extracellular vesicle.

BACKGROUND: Hyperactive neutrophil extracellular traps (NETs) formation plays a crucial role in active severe systemic lupus erythematosus (SLE). However, what triggers the imbalance in dysregulated NETs formation in SLE is elusive. Transfer RNA-derived small RNAs (tsRNAs) are novel non-coding RNAs, which participate in various cellular processes. We explore the role of tsRNAs on NETs formation in SLE. METHODS: We analyzed the levels of NETs DNA and platelet-derived extracellular vesicles (pEVs) from 50 SLE patients and 20 healthy control subjects. The effects of pEVs on NETs formation were evaluated by using immunofluorescence assay and myeloperoxidase-DNA PicoGreen assay. The regulatory mechanism of pEVs on NETs formation and inflammatory cytokines production were investigated using an in vitro cell-based assay. RESULTS: Increased circulating NETs DNA and pEVs were shown in SLE patients and were associated with disease activity (P < 0.005). We demonstrated that SLE patient-derived immune complexes (ICs) induced platelet activation, followed by pEVs release. ICs-triggered NETs formation was significantly enhanced in the presence of pEVs through Toll-like receptor (TLR) 8 activation. Increased levels of tRF-His-GTG-1 in pEVs and neutrophils of SLE patients were associated with disease activity. tRF-His-GTG-1 interacted with TLR8 to prime p47phox phosphorylation in neutrophils, resulting in reactive oxygen species production and NETs formation. Additionally, tRF-His-GTG-1 modulated NF-κB and IRF7 activation in neutrophils upon TLR8 engagement, resulting IL-1ß, IL-8, and interferon-α upregulation, respectively. CONCLUSIONS: The level of tRF-His-GTG-1 was positively correlated with NETs formation in SLE patients; tRF-His-GTG-1 inhibitor could efficiently suppress ICs-triggered NETs formation/hyperactivation, which may become a potential therapeutic target.

Neutrophils and platelets are key members in the immunopathogenesis of SLE. EVs play a key role in intercellular communication. Abnormal NETs formation promotes vascular complications and organ damage in SLE patients. tsRNA is a novel regulatory small non-coding RNA and participates in diverse pathological processes. Herein, we showed that SLE patient-derived ICs activates platelets directly, followed by intracellular tRF-His-GTG-1 upregulation, which is loaded into pEVs. The pEV-carried tRF-His-GTG-1 could interact with TLR8 in neutrophils, followed by activation of the downstream signaling pathway, including p47phox-NOX2-ROS, which causes NETs enhancement, while IRF7 promotes the expression of IFN-α. The tRF-His-GTG-1 inhibitor could suppress efficiently SLE ICs-induced NETs formation and pEVs primed NETs enhancement. This study offers new molecular machinery to explain the association between the platelets-derived tsRNAs, pEVs, and hyperactive NETs formation in lupus. tRF-His-GTG-1 may serve as a potential therapeutic target and help to advance our understanding of tsRNAs in SLE pathogenesis.

Gut microbiota regulation of T lymphocyte subsets during systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the occurrence and development of SLE by affecting the differentiation and function of intestinal immune cells. The purpose of this study was to investigate the changes of gut microbiota in SLE and judge its associations with peripheral T lymphocytes. METHODS: A total of 19 SLE patients and 16 HCs were enrolled in this study. Flow cytometry was used to detect the number of peripheral T lymphocyte subsets, and 16 s rRNA was used to detect the relative abundance of gut microbiota. Analyzed the correlation between gut microbiota with SLEDAI, ESR, ds-DNA and complement. SPSS26.0 software was used to analyze the experimental data. Mann-Whitney U test was applied to compare T lymphocyte subsets. Spearman analysis was used for calculating correlation. RESULTS: Compared with HCs, the proportions of Tregs (P = 0.001), Tfh cells (P = 0.018) and Naïve CD4 + T cells (P = 0.004) significantly decreased in SLE patients, and proportions of Th17 cells (P = 0.020) and γδT cells (P = 0.018) increased in SLE. The diversity of SLE patients were significantly decreased. Addition, there were 11 species of flora were discovered to be distinctly different in SLE group (P < 0.05). In the correlation analysis of SLE, Tregs were positively correlated with Ruminococcus2 (P = 0.042), Th17 cells were positively correlated with Megamonas (P = 0.009), γδT cells were positively correlated with Megamonas (P = 0.003) and Streptococcus (P = 0.004), Tfh cells were positively correlated with Bacteroides (P = 0.040), and Th1 cells were negatively correlated with Bifidobacterium (P = 0.005). As for clinical indicators, the level of Tregs was negatively correlated with ESR (P = 0.031), but not with C3 and C4, and the remaining cells were not significantly correlated with ESR, C3 and C4. CONCLUSION: Gut microbiota and T lymphocyte subsets of SLE changed and related to each other, which may break the immune balance and affect the occurrence and development of SLE. Therefore, it is necessary to pay attention to the changes of gut microbiota and provide new ideas for the treatment of SLE.

UNCovering new causes of monogenic systemic lupus erythematosus.

UNC93B1 is essential for the stability and endosomal trafficking of nucleic-acid sensing Toll-like receptors (TLRs) including TLR7 and TLR8. Increased TLR7 responses are associated with lupus autoimmunity in both mice and humans. In a recent article, Al-Azab et al. demonstrate the role of a variant of UNC93B1 (p.V117L) in the induction of pediatric systemic lupus erythematosus in patients and in mice through TLR7/8 hyperresponsiveness. They also highlight a potential role for the pharmacological inhibition of interleukin-1 receptor-associated kinase (IRAK) 1 and/or 4 in ameliorating disease.

Clinical, histologic, and immunologic signatures of Small Fiber Neuropathy in Systemic Lupus Erythematosus.

BACKGROUND AND OBJECTIVES: Systemic Lupus Erythematosus (SLE) often causes damage to small nerve fibers, leading to distressing painful and autonomic symptoms. Despite this, Small Fiber Neuropathy (SFN) remains an underrecognized complication for SLE patients. In this cross-sectional study, we aimed to assess SFN in patients with SLE and to explore its correlations with immunologic disease features and clinical manifestations. METHODS: We recruited 50 SLE patients (1 male to 12.5 females, aged 20-80 years) reporting painful disturbances. We conducted a comprehensive clinical and neurophysiological evaluation, using Nerve Conduction Studies and Quantitative Sensory Testing. Additionally, we carried out an extensive laboratory assessment of disease-related serological parameters. We also performed a thorough skin biopsy analysis, investigating somatic and autonomic innervation while detecting complement and inflammatory cell infiltrates within the skin. RESULTS: Out of 50 patients, 19 were diagnosed with SFN, primarily characterized by a non-length-dependent distribution; 7 had a mixed neuropathy, with both large and small fiber involvement. Patients with SFN were younger than patients with a mixed neuropathy (p = .0143); furthermore, they were more likely to have a history of hypocomplementemia (p = .0058) and to be treated with cyclosporine A (p = .0053) compared to patients without neuropathy. However, there were no significant differences in painful and autonomic symptoms between patients with and without SFN. DISCUSSION: This study highlights the relevant frequency of SFN with a non-length-dependent distribution among SLE patients experiencing painful symptoms. Indeed, SFN emerges as an early manifestation of SLE-related neuropathy and is closely associated with hypocomplementemia, suggesting a potential pathogenic role of the complement system. Moreover, SFN may be influenced by disease-modifying therapies. However, the precise role of SFN in shaping painful and autonomic symptoms in patients with SLE remains to be fully elucidated.

Retinal sublayer analysis in juvenile systemic lupus erythematosus without lupus retinopathy.

INTRODUCTION: We aimed to analyze the thicknesses of the retinal sublayer and peripapillary retinal nerve fiber layer (pRNFL) in patients with juvenile systemic lupus erythematosus (JSLE) without lupus retinopathy. METHODS: Thirty-six patients with JSLE (36 eyes) and 30 control subjects (30 eyes) were included retrospectively. Demographic data, disease duration, and clinical manifestations were recorded. Optical coherence tomography was used to examine the macula and optic disc. The thicknesses of the retina, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), and pRNFL were measured. The correlation between the thickness of retina and disease duration, erythrocyte sedimentation rate (ESR) were investigated. RESULTS: The retinal thicknesses of I3 and T3 were thinner in the JSLE group than in the control group (P = 0.019, P = 0.043, respectively). The thicknesses of the I3 and S6 sectors of the GCL decreased significantly (P = 0.013, and P = 0.022, respectively). The thickness of the S6 sector of the IPL was reduced in the JSLE group compared with the control group (P = 0.047). The JSLE group showed significant decrease in the thickness of the central sector of the ONL (P = 0.034). No statistically significant differences in INL, OPL, RPE, and pRNFL thicknesses were found. The retinal thicknesses of I3 (r = -0.386, P = 0.020) and T3 (r = -0.384, P = 0.021) presented negative associations with ESR, but had no significant correlations with disease duration. CONCLUSIONS: Retinal thinning was observed in patients with JSLE without lupus retinopathy, and this change was more pronounced in the inner layer. Key Points • Retinal thinning occurs in JSLE patients without lupus retinopathy. • Changes in retinal thicknesses are related to the ESR.

Dihydroartemisinin inhibits follicular helper T and B cells: implications for systemic lupus erythematosus treatment.

Systemic lupus erythematosus (SLE) is a common autoimmune disease, and its pathogenesis mainly involves the aberrant activation of B cells through follicular helper T (Tfh) cells to produce pathogenic antibodies, which requires more effective and safe treatment methods. Dihydroartemisinin (DHA) is the main active ingredient of artemisinin and has immunosuppressive effects. In this study, in vitro experiments confirmed that DHA inhibited Tfh cell induction and weakened its auxiliary function in B cell differentiation; furthermore, DHA directly inhibited B cell activation, differentiation, and antibody production. Furthermore, a mouse model of SLE was established, and we confirmed that DHA significantly reduced the symptoms of SLE and lupus nephritis, and decreased serum immunoglobulin (Ig)G, IgM, IgA, and anti-dsDNA levels. Moreover, DHA reduced the frequencies of total Tfh cells, activated Tfh cells, and B cell lymphoma 6, and interleukin (IL)-21 levels in Tfh cells from the spleen and lymph nodes, as well as the levels of B cells, germinal center B cells, and plasma cells in the spleen, lymph nodes, and kidneys. Additionally, DHA inhibited Tfh cells by blocking IL-2-inducible T cell kinase (ITK) signaling and its downstream nuclear factor (NF)-κB, nuclear factor of activated T cell, and activating protein-1 pathways, and directly inhibited B cells by blocking Bruton's tyrosine kinase (BTK) signaling and the downstream NF-κB and Myc pathways. Overall, our results demonstrated that DHA inhibited Tfh cells by blocking ITK signaling and also directly inhibited B cells by blocking BTK signaling. Therefore, reducing the production of pathogenic antibodies might effectively treat SLE.

Is systemic lupus erythematosus linked to Immunoglobulin G4 Autoantibodies?

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder characterized by a hyperactive immune system with multiple abnormalities in B-cell proliferation, antibody production, T-cell regulation, and immune complex (IC) formation. In humans, Immunoglobulin (Ig) G is found in four subclasses. IgG1-IgG4, which are distinguished by both structural and biological differences. Fab-arm Exchange (FAE), specific biases in the IgG4 response repertoire, and a decreased capacity to induce effector functions mediated by interactions in the fragment crystallizable (Fc) region are just a few of the distinctive characteristics of IgG4. The recent finding of the presence of double-stranded DNA (dsDNA) and antinuclear antibody (ANA)-IgG4 has raised attention to this IgG subclass and its possible role in SLE. IgG4 was previously believed to just have anti-inflammatory effects by inhibiting immune responses, but recent studies have shown that these antibodies can also play a role in the onset and development of some clinical disorders. To consider the clinical effects of IgG4 presence, it is necessary to discuss its characteristics, which could underlie the potential role it can play in SLE. Therefore, this study aimed to comprehensively review the role of IgG4 in SLE to elucidate the collective incidence of high IgG4 levels reported in some SLE patients.

Comparison of the Quantitative Values of Peripapillary, Macular and Choriocapillary Microvascular Structures According to the Presence of Lupus Nephritis in Patients with Systemic Lupus Erythematosus.

PURPOSE: To determine whether there are quantitative changes in macular, choriocapillary, and peripapillary microvascular structures using optical coherence tomography angiography (OCTA) due to the presence of lupus nephritis (LN) in patients with systemic lupus erythematosus (SLE) and to investigate the correlation between these quantitative values and disease duration. METHODS: Fifty -five patients followed up in the rheumatology clinic with an SLE diagnosis were evaluated. As the control group, 61 eyes of 61 age- and gender-matched healthy individuals were included. The patients with SLE were further divided into two groups: those with LN (29 eyes) and those without LN (26 eyes). Macular, choriocapillary, and peripapillary microvascular structures were quantitatively analyzed with OCTA and compared between the three study groups. A correlation analysis of the measured quantitative values and disease duration was also performed. RESULTS: In macular microvascular (MMV) analysis, the vessel densities (VDs) of the superficial capillary plexus (SCP) decreased in both SLE groups, while those of the deep capillary plexus (DCP) decreased only in the SLE group with LN. The foveal density significantly decreased in the SLE group with LN compared to the control group, there were no significant differences in terms of the radial peripapillary capillary VDs or the choriocapillaris flow area. Disease duration was not correlated with any of the quantitative parameters measured by OCTA in either SLE group. CONCLUSIONS: Identifying differences in retinal microvascular circulation in SLE patients with kidney damage helps predict possible nephropathy and therefore guides the treatment process of this patient.

Double-filtration plasmapheresis reduces type I interferon bioavailability and inducing activity in systemic lupus erythematosus.

Type I interferons (IFN-Is) play a significant role in systemic lupus erythematosus (SLE) pathogenesis. Double-filtration plasmapheresis (DFPP) is a treatment option for SLE; however, its effect on IFN-Is remains unclear. Therefore, we investigated the effects of DFPP on IFN-Is. Plasma from patients with SLE (n = 11) who regularly underwent DFPP was analysed using a cell-based reporter system to detect the bioavailability and inducing activity of IFN-I. The concentration of plasma dsDNA was measured, and western blotting analysis was used to assess the phosphorylation of the STING pathway. A higher IFN-I bioavailability and inducing activity were observed in patients compared to healthy controls, and both parameters decreased after DFPP. The reduction in IFN-I-inducing activity was particularly prominent in patients with high disease activity. Notably, this reduction was not observed in STING-knockout reporter cells. Additionally, plasma dsDNA levels decreased after DFPP treatment, suggesting that inhibition of the STING pathway was responsible for the observed decrease in activity. Western blotting analysis revealed suppression of STING pathway phosphorylation after DFPP. DFPP reduced IFN-I bioavailability and the inducing activity of plasma. This reduction is likely attributable to the inhibition of the STING pathway through the elimination of dsDNA.

Intercurrent infection as a risk factor for disease flares in patients with systemic lupus erythematosus.

OBJECTIVE: To determine whether intercurrent infections are a risk factor for subsequent disease flares in systemic lupus erythematosus (SLE). METHODS: Demographic and clinical characteristics of 203 patients with SLE participating in the Amsterdam SLE cohort were collected at baseline and during follow-up. Collection of data on infections and SLE flares was registry-based and infections and flares were categorised as minor or major, based on predefined criteria. Proportional hazard models with recurrent events and time-varying covariates were used to estimate the HR of SLE flares. RESULTS: The incidence rates of major and minor infections were 5.3 per 100 patient years and 63.9 per 100 patient years, respectively. The incidence rates of flares were 3.6 and 15.1 per 100 patient years for major flares and minor flares, respectively.In the proportional hazard model, intercurrent infections (major and minor combined) were associated with the occurrence of SLE flares (major and minor combined; HR 1.9, 95% CI: 1.3 to 2.9). The hazard ratio for a major SLE flare following a major infection was 7.4 (95% CI: 2.2 to 24.6). Major infections were not associated with the occurrence of minor flares. CONCLUSIONS: The results of the present study show that intercurrent infections are associated with subsequent SLE flares, which supports the hypothesis that infections may trigger SLE flares.

Longitudinally Extensive Transverse Myelitis in a Patient With Systemic Lupus Erythematosus, Recent Influenza Infection, and Nutritional Deficiencies in the Setting of Chronic Alcohol Use.

Longitudinally extensive transverse myelitis (LETM) is traditionally classified as an inflammatory disorder of the spinal cord spanning three or more vertebral segments. The differential diagnosis for TM is vast and can include infectious, nutritional, and can even be idiopathic in some reported cases. However, autoimmune etiologies such as systemic lupus erythematosus (SLE) can rarely present with neurological manifestations such as LETM. In this case report, we present a 33-year-old female with a prior history of SLE who developed an LETM in the setting of possible provoking factors such as nutritional deficiencies and a recent viral illness. In this case report, we highlight her clinical course, recovery, and working differential diagnosis after laboratory testing and neurological imaging. Finally, we discuss the different treatments that ultimately lead to her successful recovery after her prolonged clinical course.

A case report and literature review: Mycobacterium leprae infection diagnosed by metagenomic next-generation sequencing of cerebrospinal fluid.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) that is responsible for deformities and irreversible peripheral nerve damage and has a broad spectrum of clinical and serological manifestations. Leprosy primarily affects the peripheral nerves and rarely presents with central nervous system involvement. Diagnosing leprosy can still be difficult in some cases, especially when the infection involves uncommon clinical manifestations and extracutaneous sites. Delayed diagnosis and treatment of leprosy may lead to irreversible damage and death. CASE PRESENTATION: We report a case of a 30-year-old female presenting with "repeated high fever with symptoms of headache for 14 days". On the day of admission, physical signs of lost eyebrows and scattered red induration patches all over her body were observed. The patient's diagnosis was based on the clinical characteristics using a combination of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and slit-skin smear. After confirming Listeria meningitis and multibacillary leprosy with erythema nodosum leprosum (ENL), a type 2 reaction, she was treated with ampicillin sodium, dapsone, rifampicin, clofazimine, methylprednisolone, and thalidomide. At the 1-year follow-up, the frequency and severity of headaches have significantly decreased and a good clinical response with improved skin lesions was found. CONCLUSION: This case highlights the importance of considering leprosy, which is a rare and underrecognized disease, in the differential diagnosis of skin rashes with rheumatic manifestations, even in areas where the disease is not endemic, and physicians should be alerted about the possibility of central nervous system infections. In addition, mNGS can be used as a complementary diagnostic tool to traditional diagnostic methods to enhance the diagnostic accuracy of leprosy.

Unilateral Pleural Effusion as an Initial Manifestation of Systemic Lupus Erythematosus in a Patient of Advanced Age.

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease that can manifest in older individuals, presenting unique diagnostic challenges because of its atypical presentations and comorbidities. Pleural effusion is a relatively uncommon manifestation of SLE, with studies suggesting a higher prevalence in older than younger patients. We herein report an atypical case of delayed-onset SLE in a 75-year-old man with left-sided pleural effusion as the initial presentation. This case underscores the difficulty of diagnosing SLE in patients of advanced age and the importance of considering a broad range of differential diagnoses, even in cases that may suggest a more common disease. This case also highlights the fact that unilateral pleural effusion can be an initial manifestation of SLE, and when the cause of the pleural effusion is unclear, SLE should be considered as a potential diagnosis.