Overlap syndrome is a rare condition involving the coexistence of at least two distinct autoimmune diseases, such as systemic lupus erythematosus and systemic sclerosis. This condition has limited studies on epidemiology probably because it is often under-recognized. We present a 22-year-old Filipino female with a 10-month history of hyperpigmented patches on the malar surface and extremities, with associated photosensitivity, fatigue, pallor, arthralgia, and oral ulcers, and positive antinuclear antibody titer. She was treated with oral Prednisone in tapering doses, leading to clinical improvement. Eight months later, there was a recurrence of hyperpigmented patches on the face and extremities with skin tightening and diffuse hair loss, development of shiny skin with facial fold loss, a beak-like nasal appearance, and episodes of dyspnea and malaise. Consistent with scleroderma, the patient was started on mycophenolate mofetil (MMF) 500 mg daily, with close monitoring for disease progression and systemic involvement. Overlap syndrome remains under-recognized due to its variable presentation and rarity. Treatment is individualized based on the specific connective tissue diseases involved and the patient’s symptoms. Multidisciplinary care is crucial for timely management and to adjust treatment as needed, given the potential for life-threatening complications involving cutaneous and internal organs.

Systemic Lupus erythematosus (SLE) is a multiorgan autoimmune disease that affects 20-150 per 100,000 women. It is a mutagenic disease which causes formation of autoantibodies immune complexes that leads to inflammation in different organs leading to organ damage. We present a case of a young female who was newly diagnosed to have SLE. She presented with an elevated ANA, low C3 and elevated Anti-DS DNA. She first manifested with epistaxis and subsequently experienced the various complications of SLE such as infection, thrombosis, bleeding, ascites, etc. The initial presentation of normochromic, normocytic anemia and thrombocytopenia together with further work-ups supported another concomitant autoimmune disease, namely Evan’s syndrome. Evan’s syndrome is a rare manifestation of SLE, and is observed in only 2.73% of the population. In addition, the patient manifested with sudden onset of right-sided body weakness with Cranial CT scan findings of areas of focal infarction in the frontal lobe with concomitant acute intracranial hemorrhages. The evidence of both thrombosis and hemorrhage provided conflicting management strategies for this patient. The use of hydroxychloroquine, which is the cornerstone of lupus therapy, provided beneficial antithrombotic effects. A multidisciplinary approach to management and prudent choice of medications were vital in the success of treatment on such a complicated case.

Objective: To determine the one-year outcomes of newly-diagnosed patients with systemic lupus erythematosus (SLE) in a tertiary government hospital in Manila, Philippines. Methods: After ethics approval, we reviewed the medical records of a cohort of 44 newly-diagnosed SLE patients at 6- and 12-months post-diagnosis in 2018-2019. The outcomes of interest were: modified lupus low disease activity state as defined (mLLDAS), remission, hospitalization, 30-day readmission, organ damage, and mortality. Results: The patients were predominantly young females (mean age of 29 ± 9.9 years). There was an average interval period of six months between onset of symptoms and diagnosis (6.4 ± 10.8 months). The most common manifestations were mucocutaneous (86.4%), hematologic (63.6%), musculoskeletal (61.4%), and renal disorder (47.7%). There was at least one positive serologic test in 88.7%. Five patients (11.4%) had comorbidity, usually hypertension (9.1%). The initial lupus treatment consisted of moderate to high doses of glucocorticoids and hydroxychloroquine. Patients with life-threatening or organ-threatening disease, usually nephritis, received cyclophosphamide, azathioprine, or mycophenolate mofetil. One patient received rituximab. Fewer patients with nephritis received cyclophosphamide infusions during the first six months compared to the later six months. Most of the hospitalizations (34/36) occurred during the first six months and 22 of these were for diagnosis. Seven patients had more than one hospitalization and five (20%) had 30-day readmissions. mLLDAS was achieved by 15 (34.1%) and 30 (68.2%) patients at 6- and 12- months, respectively. Only one patient was in remission a year after diagnosis. Seven patients (15.9%) were assessed with organ damage, six (13.64%) of them at 6-months post-diagnosis. Organ damage was most commonly renal. Four (9.1%) patients died, all during their initial hospitalization. Conclusion In our population observed over a period of one year (2018-2019), there was a very low rate of remission (1/44, 2.3%), mLLDAS in 68.2%, and organ damage in 15.9%. Most of the hospitalizations (65%) were for the diagnosis of lupus and all deaths (9.1%) occurred during this first hospital confinement. We must intensify our efforts to (1) achieve earlier diagnosis, (2) deliver optimal lupus treatment and supportive care during the first lupus hospitalization, and (3) initiate early and persistent immunosuppressive treatment for nephritis to improve outcomes for our patents with SLE.
Lupus Erythematosus, Systemic ; Hospitalization ; Philippines

Humans ; Lupus Vasculitis, Central Nervous System/pathology* ; Magnetic Resonance Imaging/methods* ; Diffusion Tensor Imaging/methods* ; Patients ; Lupus Erythematosus, Systemic/pathology* ; Brain/pathology*

Objective To evaluate the correlation between alterations in DNase1 and DNase1L3 enzyme activities and impairment of NET degradation in patients with sporadic SLE, and to investigate the underlying mechanism. Methods 46 sporadic SLE patients and 30 age- and sex-matched healthy individuals were recruited. Serum levels of DNase1, DNase1L3 and corresponding autoantibodies were detected by ELISA. DNase1 and DNase1L3 were isolated by immunoprecipitation; NETs and enzyme degradation activities were detected using a modified immunofluorescence. DNase1L3 secretion by PBMCs was analyzed by ELISPOT, Western blotting and reverse transcription PCR. Results Levels of H3-dsDNA and Ela-dsDNA complexes were significantly elevated in SLE patients. LDGs in SLE population was significantly higher than in the control group, and LDGs was positively correlated with H3-dsDNA and Ela-dsDNA NETs complexes. The ability of SLE patients to degrade NET in vitro was significantly lower than that of the control group. Degradation experiments of DNase1 and DNase1L3 in different proportions showed that the decrease in DNase1L3 activity was the primary contributor to the elevated NET residue level. The concentration of DNase1L3 autoantibodies in SLE patients was significantly elevated compared to the control group. In addition, the capacity of PBMCs to secrete DNase1L3 was significantly lower in the SLE patients compared to the control group. Conclusion Decreased secretion of DNase1L3 and the presence of relevant autoantibodies notably impede NET degradation in patients with SLE, offering new directions for the monitoring and treatment of SLE patients.
Humans ; Autoantibodies ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Extracellular Traps ; Lupus Erythematosus, Systemic

Discoid Lupus Erythematosus (DLE) is the most common form of chronic cutaneous Lupus Erythematosus (LE). Characteristic lesions cause disfigurement impacting quality of life, with 5% of progress into systemic LE (SLE). Prompt diagnosis avoids sequelae such as scarring, recurrence, and malignancy. Local therapy includes sun protection, steroids, and calcineurin inhibitors (CNIs). Antimalarials and surgical or cosmetic interventions are other options.

Glioblastoma multiforme (GBM) represents the most malignant form of brain tumor and is relatively common, comprising nearly almost 20% of all primary malignancies of the central nervous system1. GBM is a WHO grade IV tumor with several variants, depending primarily on their genetic signature and on the predominant histological architecture. Among the variants of GBM, epithelioid glioblastoma (E-GBM) has been one of the more recently described. This tumor, documented to be highly malignant and clinically aggressive, has been separated from close variants and thus differentials, pleomorphic anaplastic xanthoastrocytoma, rhabdoid GBM, small cell and giant cell GBM, GBM with neuroectodermal differentiation, and gliosarcoma2. Autoimmune diseases have been linked within creased risk of CNS complications, from the constant effects of chronic inflammatory milieu. Systemic lupus erythematosus (SLE) has been associated with several CNS abnormalities, hence the terms CNS lupus or neuropsychiatric lupus. Likewise, SLE has been repeatedly associated with CNS malignancies in several cases and case reports. To date, there is paucity in the reported cases of malignant brain tumors, especially rare variants, in patients with SLE. While it is hypothesized that the inflammatory milieu that bathes the brain in a dynamic microenvironment that influences the incidence of rare variants of GBM, clinicians should be mindful, as treatment is challenging: it may either induce exacerbation of autoimmunity or cause undertreatment of the malignancy. This complex interplay births curiosity into the enigma of autoimmunity and oncology. In this particular report, we highlight the case of a patient with SLE who developed E-GBM. We identify the clinicopathologic features of the tumor present in the patient and explore the known aspects of the crosstalk between SLE and E-GBM.
Lupus Erythematosus, Systemic ; Glioblastoma

INTRODUCTION

Macrophage Activation Syndrome (MAS) is a rare but life threatening pro-inflammatory complication of multiple autoimmune diseases leading to cytokine storm. We report a case of MAS as a presenting manifestation of Systemic Lupus Erythematosus.

A 32-year-old female, newly diagnosed with Systemic Lupus Erythematosus (SLE), presents with a 3-month history of fever and joint pains, which began a few days after receiving her first dose of a viral vector COVID-19 vaccine. She later developed facial edema, and her fever became persistent and unremitting. Upon presentation, she was initially hypotensive, tachycardic, with distended neck veins, with periorbital edema and muffled heart sounds. Initial work-up revealed pericardial effusion, anemia, thrombocytopenia, elevated creatinine, hypoalbuminemia, hematuria, and pyuria. She was intubated, started on inotrope, and underwent pericardiocentesis. Patient was classified as SLE based on Systemic Lupus International Collaborating Clinics Classification (SLICC) Criteria despite negative antinuclear antibody (ANA). Nevertheless, she was started on IV steroids and hydroxychloroquine. She was eventually extubated after significant clinical improvement. Further work-up for MAS was however done due to persistent febrile episodes. Hyperferritinemia, hypertriglyceridemia, hypercholesterolemia, pancytopenia, transaminitis, and splenomegaly on imaging were noted. She was then started on methylprednisolone pulse therapy. After treatment, marked clinical improvement, as well as resolution of transaminitis and pancytopenia were noted.

A high index of suspicion for MAS should exist in a patient with pyrexia of unknown origin with concomitant autoimmune disease. In this disease that can lead to progressive organ failure, early diagnosis and management is crucial. This case report culminates the need for diagnostic and therapeutic guidelines that will help in the early diagnosis and immediate treatment of this debilitating condition.

Objective: To explore the causal effects of the serum Vitamin D levels on the risk of systemic lupus erythematosus (SLE). Methods: A two-sample Mendelian randomization (MR) study was performed to infer the causality. Three Genome-wide association studies (GWAS) for circulating Vitamin D levels, including 25-hydroxyvitamin D [25(OH)D], 25-hydroxyvitamin D₃ [25(OH)D₃] and C3-epimer of 25-hydroxyvitamin D₃ [C3-epi-25(OH)D₃] published in 2020, and one GWAS for SLE published in 2015 were utilized to analyze the causal effects of the serum Vitamin D levels on the risk of SLE. MR analyses were conducted using the inverse-variance weighted method (IVW), weighted median, MR-Egger methods, MR-pleiotropy residual sum and outlier (MR-PRESSO) method. Results: 34, 29 and 6 SNPs were respectively selected as instrumental variables to analyze the causal association of total 25 (OH) D level, 25 (OH) D₃ level and C3-epi-25 (OH) D₃ level with the risk of SLE. The MR results showed that each standard deviation decrease in the level of 25(OH)D₃ would result in 14.2% higher risk of SLE (OR, 0.858; 95%CI, 0.753-0.978; P=0.022). The levels of 25(OH)D and C3-epi-25(OH)D₃ had null associations with risk of SLE (OR, 0.849; 95%CI, 0.653-1.104; P=0.222; OR, 0.904; 95%CI, 0.695-1.176; P=0.452). Conclusion: This study have identified a causal effect of 25(OH)D₃ on increased risk of SLE. These findings highlighted the significance of active monitoring and prevention of SLE in population of low Vitamin D levels.
Humans ; Genome-Wide Association Study ; Vitamin D ; Lupus Erythematosus, Systemic/complications* ; Vitamins ; Causality ; Mendelian Randomization Analysis/methods* ; Polymorphism, Single Nucleotide

Humans ; Child ; Klinefelter Syndrome/complications* ; Lupus Erythematosus, Systemic/complications*