Coinfection of Klebsiella pneumoniae and Aspergillus in a patient with chronic obstructive pulmonary disease post cardiac arrest: a case report.

INTRODUCTION: Chronic obstructive pulmonary disease is a lung condition characterized by chronic respiratory symptoms (breathlessness, cough, and expectoration). In the advanced stages, patients often report to the Accident & Emergency department due to worsening of symptoms. Because of the repeated exposure to corticosteroids during the management of exacerbations, these patients are susceptible to super additional infections. Pulmonary aspergillosis can be divided into three main categories: invasive pulmonary aspergillosis, allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. Aspergillus overlap syndrome is defined as the presence of more than one form of Aspergillus in a single patient. However, coinfection with Klebsiella and pulmonary aspergillosis overlap syndrome is rare and poses a treatment challenge. As per a pub med search, no such case report has been reported in a case of chronic obstructive pulmonary disease. CASE REPORT: We report the case of a 66-year-old male, Punjabi Hindu by ethnicity, who was a reformed smoker with a known case of COPD. He presented with a history of breathlessness (mMRC grade 4) associated with cough with expectoration and wheezing for 15 days and intermittent episodes of hemoptysis for more than 6 months. The examination revealed tachypnea and wheezing throughout the lung fields. He was initially managed with parenteral steroids and frequent nebulization with bronchodilators. On day 5 of hospitalization, the patient experienced worsening of symptoms and cardiac arrest; he was intubated and return of spontaneous circulation was achieved within 5 minutes of cardio pulmonary resuscitation. Tracheal aspirate and culture revealed Aspergillus fumigatus and Klebsiella pneumoniae respectively. He underwent chest CT, which showed features suggestive of allergic bronchopulmonary aspergillosis and invasive pulmonary aspergillosis. He was found to have elevated ß-D-glucan, galactomannan, and aspergillus IgE and IgG. Severe pneumonia and pulmonary Aspergillus overlap syndrome were managed with antibiotics, steroids, and antifungals. Over the next 15-20 days, his general condition improved. He was discharged after 45 days of hospitalization and continued on oral corticosteroids, antifungals, and inhaled bronchodilators. CONCLUSION: Coinfection with bacteria and fungi worsens the outcome. Clinicians should be aware of the polymicrobial manifestations and various drug interactions involved. Timely diagnosis aids in better management strategies and improved patient outcomes.

Prognostic efficacy of non-invasive ventilation in patients with overlap syndrome: chronic obstructive pulmonary disease and obstructive sleep apnea.

Background: Limited evidence exists regarding the effects of non-invasive ventilation (NIV) on the prognosis of patients with concomitant chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), also known as overlap syndrome (OS). This study aimed to assess whether NIV alongside standard care could improve the prognosis of this cohort. Methods: We retrospectively collected data from 229 patients with severe OS treated in Beijing Anzhen Hospital between January 1, 2016 and January 1, 2020, with follow-up until December 1, 2023. All patients were recommended usual care and NIV and were subsequently divided into non-NIV (usual care only) and NIV groups (usual care plus NIV) per their willingness and adherence to NIV. Endpoints included all-cause and acute exacerbation of COPD (AECOPD)-associated death and re-hospitalization. Multivariate analyses were used to determine the relationship of NIV with prognosis. Results: The follow-up lasted for a median of 760 days (interquartile range, 245-1,374 days). Patients in the NIV group showed lower rates of all-cause (37.5% vs. 65.1%, P<0.001) and AECOPD-associated (31.7% vs. 58.7%, P<0.001) death compared with patients in the non-NIV group. Compared with usual care only, NIV treatment was associated with significant reduction in all-cause death [relative risks (RR) =0.459, 95% confidence interval (CI): 0.315-0.668, P<0.001], AECOPD-associated mortality (RR =0.424, 95% CI: 0.283-0.635, P<0.001), and re-hospitalization for all causes (RR =0.455, 95% CI: 0.342-0.605, P<0.001) and for AECOPD (RR =0.421, 95% CI: 0.308-0.575, P<0.001) in Cox hazards models, with significance persisting after multivariable adjustment. Conclusions: NIV may improve outcomes and survival in patients with severe OS of comorbid COPD and OSA. Confirmatory studies are needed to prove benefits.

Systematic analysis of SCN5A variants associated with inherited cardiac diseases.

BACKGROUND: SCN5A variants are associated with a spectrum of cardiac electrical disorders with clear phenotypes. However, they may also be associated with complex phenotypic traits like overlap syndromes or pleiotropy, which have not been systematically described. In addition, the involvement of SCN5A in dilated cardiomyopathies (DCMs) remains controversial. OBJECTIVE: We aimed to evaluate the different phenotypes associated with pathogenic (P)/likely pathogenic (LP) SCN5A variants and to determine the prevalence of pleiotropy in a large multicentric cohort of P/LP SCN5A variant carriers. METHODS: The DNA of 13,510 consecutive probands (9960 with cardiomyopathies) was sequenced with a custom panel of genes. Individuals carrying a heterozygous single P/LP SCN5A variant were selected and phenotyped. RESULTS: The study included 170 P/LP variants found in 495 patients. Of them, 119 (70%) were exclusively associated with a single well-established phenotype: 91 with Brugada syndrome, 15 with type 3 long QT syndrome, 6 with progressive cardiac conduction disease, 4 with multifocal ectopic Purkinje-related premature contractions, and 3 with sick sinus syndrome. Thirty-two variants (19%) were associated with overlap syndromes or pleiotropy. The 19 remaining variants (11%) were associated with atypical or unclear phenotypes. Of those, 8 were carried by 8 patients presenting with DCM with a debatable causative genotype/phenotype link. CONCLUSION: Most P/LP SCN5A variants were found in patients with primary electrical disorders, mainly Brugada syndrome. Nearly 20% were associated with overlap syndromes or pleiotropy, underscoring the need for comprehensive phenotypic evaluation. The concept of SCN5A variants causing DCM is extremely rare (8/9960) if not questionable.

Clinical characteristics of primary biliary cirrhosis - idiopathic inflammatory myopathy overlap syndrome: A single center study.

PURPOSE: Primary biliary cirrhosis-idiopathic inflammatory myopathy (PBC-IIM) overlap syndrome (OS) is a rare condition in which cardiac involvement is observed. We aimed to characterize the clinical features and associated factors of PBC-IIM OS patients with cardiac involvement. METHODS: Patients with PBC-IIM OS that visited our hospital from January 1983 to December 2021 were enrolled. Clinical presentations and laboratory and imaging data were recorded. The clinical data of patients with and without cardiac involvement were compared. According to the first instance of a disease flare, prognostic factors were also studied. RESULTS: Thirty-four patients with PBC-IIM OS were enrolled. A total of 58.8% of patients presented with muscle weakness at disease onset, which primarily involved skeletal muscle (85.3%). Slight liver dysfunction was discovered in this OS cohort. In patients with cardiac involvement, palpitation (63.6%) and dyspnea (36.4%) were the most common onset symptoms. Arrhythmia was a vital manifestation in OS patients, in which half of OS patients had nonsustained ventricular tachycardia (50.0%, 11/22). Compared with noncardiac involvement, myalgia (4.5%, P = 0.004) and fever (0.0%, P = 0.011) were reported relatively rarely at disease onset in the group with cardiac involvement. The prognosis analysis showed that positivity for anti-Ro52 (HR=0.00, P = 0.034) negatively correlated with relapse in OS patients. CONCLUSION: PBC-IIM OS has unique features. Typical clinical manifestations and early worsening cardiac indicators can be used to identify cardiac involvement and predict prognosis. Anti-Ro52 may have prognostic value for PBC-IIM OS.

The implication of anti-Ro60 with or without anti-Ro52 antibody in patients with systemic lupus erythematosus.

OBJECTIVES: Anti-Ro60 and anti-Ro52 autoantibodies are frequently used as diagnostic biomarkers for Sjogren's disease, but their clinical significance in systemic lupus erythematosus (SLE) is not well characterised. METHODS: Patients fulfilling SLE classification criteria were studied according to their anti-Ro status. We defined Ro positivity (Ro+) as those who have either anti-Ro60 or anti-Ro52 positivity. Patient characteristics and disease outcomes, including High Disease Activity Status (HDAS) defined as an ever attainment of SLEDAI2K ≥10, adjusted mean SLEDAI (AMS), and time-adjusted mean clinical SLEDAI (excluding serologic activities) were compared using linear or logistic regressions. Furthermore, isolated or dual positivity of anti-Ro60 and anti-Ro52 were studied. RESULTS: Out of 409 patients, 47.2% were Ro+. Ro+ patients were predominantly Asian, had positive dsDNA and hypocomplementemia. They showed a higher likelihood of HDAS (OR 1.65, 95% CI 1.10-2.48, p= 0.015), AMS > 4 (OR 1.84, 1.18-2.88, p= 0.007), and more frequent use of glucocorticoids (OR 1.87, 1.16-3.03, p= 0.011) and immunosuppressants (OR 2.0, 1.26-3.17, p= 0.003). Additionally, 24.4% of Ro+ patients experienced sicca symptoms, and hypergammaglobulinemia was significantly more common. Multivariate analysis confirmed that Asian ethnicity, severe flares, AMS, hypocomplementemia, rheumatoid factor, proteinuria, leucopenia, and sicca symptoms were significantly linked to Ro positivity. CONCLUSION: Anti-Ro positivity is associated with higher disease activity and increased treatment needs. Ro positivity correlates with laboratory abnormalities such as hypocomplementemia and leucopenia. These findings highlight the importance of anti-Ro60/Ro52 testing in the clinical evaluation of SLE.

Risk factors analysis of noninvasive positive pressure ventilation in inpatients with overlapping syndrome of chronic obstructive pulmonary disease combined with obstructive sleep apnea.

OBJECTIVE: The aim of the study was to analyze the clinical data of patients with chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome (OS) during hospitalization and to evaluate the risk factors of patients treated with Non-Invasive Ventilation (NIV). METHODS: Demographic and clinical data of patients with confirmed OS during hospitalization were retrospectively collected. The patients were divided into two groups according to whether noninvasive ventilator was used during hospitalization, including OS treated with NIV (244 cases) and OS without NIV (239 cases). The t-test, χ 2 test, and Kaplan-Meier curve were used to compare the two groups, and multiple logistic regression was used to analyze the risk factors of NIV in patients with OS. RESULTS: Compared with the OS group without NIV, the pulmonary hypertension, lymphocyte count, and left ventricular ejection fraction% of OS patients with NIV were lower, whereas PCO2, uric acid, C-reactive protein, procalcitonin, and N-terminal pro-B-type natriuretic peptide were higher, with statistical differences (P < 0.05). During hospitalization and follow-up, OS patients with NIV had a longer hospital stay (P < 0.001), and there was no significant difference in the rate of readmission within 28 days. The logistic regression analysis showed that the history of diuretic use, previous history of noninvasive ventilator use, and ischemic heart disease were independent risk factors for NIV treatment in OS patients during hospitalization. CONCLUSION: Patients with OS undergoing NIV during hospitalization exhibited more severe overall illness and had prolonged hospital stays compared to OS patients not receiving NIV. History of diuretic use, history of NIV use, and ischemic heart disease are independent risk factors for NIV treatment in OS patients during hospitalization.

Lamotrigine Emerging as a Driver of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: An 8-Year Retrospective Study.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent severe manifestations of a potentially life-threatening spectrum defined by a desquamating rash of the skin and mucous membranes. This study was prompted by the observed increase in the off-label use of lamotrigine as a causal agent in SJS/TEN in our regional burn center. METHODS: A retrospective cohort of 48 patients presenting to the Connecticut Burn Center from 2015-2022 with suspicion for SJS/TEN were reviewed for age, sex, causative drug, presenting symptoms, hospital course, biopsy confirmation, length of stay, comorbidities, and 30-day mortality. Descriptive statistical analysis was conducted to identify trends in causative agent, clinical presentation, and mortality. RESULTS: Thirty patients in our cohort received a final diagnosis of SJS/TEN. While antibiotics remain the most frequent cause of SJS/TEN across the study period (33.3 %, n = 10), the incidence of cases attributable to lamotrigine increased from 1 case between 2015 and 2018 (6.7 %) to 6 cases between 2019 and 2022 (40 %). In 2020 alone, 50 % of all cases were attributable to lamotrigine (n = 4). Of the patients where lamotrigine was implicated, 71.4 % (n = 5) were prescribed lamotrigine for off-label use in the treatment of non-bipolar mood disorders. The average lamotrigine-associated SJS/TEN patient was younger (p < 0.001), had fewer comorbidities, and was more likely to be female than the general SJS/TEN population. CONCLUSION: Off-label use of lamotrigine is emerging as a major driver of SJS/TEN with notable changes in patient demographics. Further research is necessary to understand how changing trends in the patient population will impact clinical course and optimal management.

Protocol for a randomized controlled trial of moderate intensity interval training in individuals with chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome who have excessive daytime sleepiness.

BACKGROUND: The term "Overlap Syndrome" (OS) describes the presence of both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) in a single individual. Excessive daytime sleepiness (EDS) is a common symptom of OS shown to be associated with an increased risk of cardiovascular disease (CVD) that could be reduced through exercise. Thus, we propose to investigate a novel exercise intervention in individuals with the EDS-OS phenotype as they are at highest risk of CVD yet have the greatest barriers to exercise. METHODS: We will conduct a single-site, randomized, two-arm, parallel group-controlled exercise trial in individuals with EDS-OS. The Epworth Sleepiness Scale (ESS) will be assessed at baseline. Individuals with OS and the EDS-OS phenotype (ESS >10) (n = 46) will be randomized to a moderate intensity interval training (MIIT, i.e. intervals of 5 min at 50% VO2peak followed by 3 min of active recovery at 10% VO2peak) or a control group of standard of care. We will investigate if MIIT intervention decreases the risk of CVD in EDS-OS, which will be assessed by: 1) quality of life, measured by the 36-Item Short Form Health Survey; 2) physical activity, measured by daily step counts; and 3) cardiovascular health, assessed as VO2peak, flow-mediated dilation and serum high sensitivity C-reactive protein, lipids, and glucose. CONCLUSION: Our findings will guide future development and implementation of exercise interventions that could reduce the risk of CVD in the understudied EDS-OS phenotype.

Evolution from viral encephalitis to autoimmune encephalitis to multiple sclerosis: a case report.

BACKGROUND: There are established associations between viral and autoimmune encephalitis as well as between autoimmune encephalitis and demyelinating central nervous system (CNS) diseases. Here, we report the evolution from varicella zoster virus (VZV) encephalitis to limbic autoimmune encephalitis (AIE) to multiple sclerosis (MS) in one patient. CASE REPORT: A woman in her mid-thirties presented with headache, aphasia, and a generalized tonic-clonic seizure. Cerebrospinal fluid (CSF) VZV polymerase chain reaction was positive and treatment with acyclovir was administered for VZV encephalitis. Five months later, the patient presented with cognitive deficits and MRI showed new bilateral hippocampal T2-hyperintensities. CSF analyses revealed pleocytosis and neuropil antibodies in tissue-staining. A diagnosis of limbic AIE was established and treatment with IV steroids and IV immunoglobulins initiated. One year later, the patient developed paresthesia of both legs and magnetic resonance imaging studies now showed new supratentorial and spinal demyelinating lesions. The patient was diagnosed with MS and treatment was changed to rituximab. CONCLUSIONS: This unique case report links three important neuroimmunological entities in characterizing the evolution from infectious to autoimmune encephalitis to multiple sclerosis in one patient. Identification of such rare clinical constellations is critical for correct treatment choice and provides important novel insights into the pathophysiology of neuroimmunological disorders including viral triggers and overlap manifestations of autoimmune CNS diseases.

Assessment of Chronic Hypercapnic Respiratory Failure.

Undiagnosed chronic hypercapnic respiratory failure may be encountered during the evaluation of sleep-related breathing disorders at the sleep clinic. This article reviews the mechanism of chronic hypercapnic respiratory failure and the systematic approach to the assessment of specific sleep disorders associated with nocturnal hypoventilation encountered in clinical practice.

Undercover lung damage in pediatrics - a hot spot in morbidity caused by collagenoses.

Connective tissue represents the support matrix and the connection between tissues and organs. In its composition, collagen, the major structural protein, is the main component of the skin, bones, tendons and ligaments. Especially at the pediatric age, its damage in the context of pathologies such as systemic lupus erythematosus, scleroderma or dermatomyositis can have a significant negative impact on the development and optimal functioning of the body. The consequences can extend to various structures (e.g., joints, skin, eyes, lungs, heart, kidneys). Of these, we retain and reveal later in our manuscript, mainly the respiratory involvement. Manifested in various forms that can damage the chest wall, pleura, interstitium or vascularization, lung damage in pediatric systemic inflammatory diseases is underdeveloped in the literature compared to that described in adults. Under the threat of severe evolution, sometimes rapidly progressive and leading to death, it is necessary to increase the popularization of information aimed at physiopathological triggering and maintenance mechanisms, diagnostic means, and therapeutic directions among medical specialists. In addition, we emphasize the need for interdisciplinary collaboration, especially between pediatricians, rheumatologists, infectious disease specialists, pulmonologists, and immunologists. Through our narrative review we aimed to bring up to date, in a concise and easy to assimilate, general principles regarding the pulmonary impact of collagenoses using the most recent articles published in international libraries, duplicated by previous articles, of reference for the targeted pathologies.

Kikuchi-Fujimoto Disease Preceding Overlap Syndrome of Sjögren's Syndrome and Systemic Lupus Erythematosus: Literature Review Based on a Case Report.

Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting histiocytic necrotizing lymphadenitis systemic disorder with unknown etiology. KFD has been known for half a century, but difficulties in distinguishing it remain. Its diagnostic significance is related to the increasing prevalence of KFD with autoimmune diseases in various timeframes. Systemic lupus erythematosus (SLE) is the most prevalent autoimmune connective tissue disease (AICTD) appearing alongside KFD. An 18-year-old female presented with acute muscle weakness, shortness of breath, fever, and significant weight loss for 5 months before admission. Pain and morning joint stiffness had been felt for 9 months. One year ago, she lumped her right neck and was diagnosed with KFD from the excision biopsy and immunohistochemical staining (CD68). Creatine-kinase enzymes and C-Reactive protein were elevated with a high anti-Ku and anti-Jo-1 negative level. There was a low level of complements, high anti-nuclear antibody titer, with positive anti-SS-A. Sialometry and Schirmer test showed reduced salivary and lacrimal gland production. We diagnosed this patient as having an overlap syndrome preceded by KFD. The AICTD involved was Sjögren's syndrome and SLE. Although KFD is considered a self-limiting disease, its occurrence should be noticed regarding the possibility of other autoimmune conditions. KFD usually coincides with AICTD, although it could also precede or occur afterward. This case is reported to raise awareness of the overlap syndrome preceded by KFD.

Myasthenia gravis Lambert-Eaton overlap syndrome: Recommended modification for the diagnostic criteria.

In 2016, MLOS (myasthenia gravis Lambert-Eaton overlap syndrome) was coined to represent an entity of overlap syndrome of myasthenia gravis and Lambert-Eaton myasthenic syndrome. Fifty-five MLOS patients have been identified. Modification of the diagnostic criteria for MG by adding MuSK positive antibody testing is recommended. Two MuSK positive MLOS patients were identified by the new diagnostic criteria.

Chronic obstructive pulmonary disease and obstructive sleep apnea overlap: who to treat and how?

INTRODUCTION: The co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), or the overlap syndrome, is common and associated with a distinct pattern of nocturnal hypoxemia and worse clinical outcomes than either disease alone. Consequently, identifying who and how to treat these patients is essential. AREAS COVERED: Treatment is recommended in all patients with OSA and symptoms or systemic hypertension, but determining symptoms attributable to OSA can be challenging in patients with COPD. Treatment should be considered in asymptomatic patients with moderate to severe OSA and COPD with pulmonary hypertension and comorbid cardiovascular and cerebrovascular disease, especially if marked hypoxic burden. CPAP is effective, but in patients with the overlap syndrome and daytime hypercapnia, high-intensity noninvasive ventilation aiming to lower PaCO2 may have additional benefits. Additionally, in those with severe resting daytime hypoxemia, supplemental oxygen improves survival and should be added to positive airway pressure. The role of alternative non-positive airway pressure therapies in the overlap syndrome needs further study. EXPERT OPINION: Both COPD and OSA are heterogeneous disorders with a wide range of disease severity and further research is needed to better characterize and prognosticate patients with the overlap syndrome to personalize treatment.

Acute renal failure caused by Sjögren's syndrome and rheumatoid arthritis overlap syndrome.

Introduction: Sjögren's syndrome (SS) and rheumatoid arthritis (RA) are two chronic autoimmune diseases. To date, there have been few reports on the overlap between SS and RA in China, especially regarding correlated acute renal failure cases. Methods: To provide a reference for our clinical peers, this article presents the case report of an elderly female patient who was diagnosed with acute renal failure caused by SS and RA overlap syndrome. Results: We also provide a relevant analysis of SS and RA overlap syndrome treatment. Conclusions: We also provide a relevant analysis of SS and RA overlap syndrome treatment.

A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report.

Pseudohypoparathyroidism (PHP) type 1a (PHP 1a) is a rare hereditary disorder characterized by target organ resistance to hormonal signaling and the Albright hereditary osteodystrophy (AHO) phenotype, which features round facial features, short fingers, subcutaneous calcifications, short stature, obesity, and intellectual disability. Progressive osseous heteroplasia (POH) is another rare disorder characterized by heterotopic ossification (HO) that progressively affects skin, subcutaneous tissues, and deep skeletal muscle. PHP 1a is inherited maternally due to a GNAS mutation, while pure POH is inherited paternally. This case study presented a Chinese boy with congenital hypothyroidism, tonic-clonic seizures, hypoparathyroidism, AHO, POH, and joint fixation deformity. Sequencing analysis of GNAS-Gsα revealed a heterozygous C.432+2T>C(P.?) variant (NM_000516.7) affecting the canonical splice donor site of intron 5 in the boy and his mother, indicating maternal inheritance of a GNAS mutation. The patient was diagnosed with POH overlap syndrome (POH/PHP 1a). Following calcium and calcitriol supplementation, he experienced a reduction in seizures, and surgery was performed to correct the joint fixation deformity caused by HO. This case report provided valuable insights into the genotype-phenotype correlations of POH overlap syndrome and underscored the significance of genetic testing in diagnosing rare diseases.

Anti-Ku + myositis: an acquired inflammatory protein-aggregate myopathy.

Myositis with anti-Ku-autoantibodies is a rare inflammatory myopathy associated with various connective tissue diseases. Histopathological studies have identified inflammatory and necrotizing aspects, but a precise morphological analysis and pathomechanistic disease model are lacking. We therefore aimed to carry out an in-depth morpho-molecular analysis to uncover possible pathomechanisms. Muscle biopsy specimens from 26 patients with anti-Ku-antibodies and unequivocal myositis were analyzed by immunohistochemistry, immunofluorescence, transcriptomics, and proteomics and compared to biopsy specimens of non-disease controls, immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Clinical findings and laboratory parameters were evaluated retrospectively and correlated with morphological and molecular features. Patients were mainly female (92%) with a median age of 56.5 years. Isolated myositis and overlap with systemic sclerosis were reported in 31%, respectively. Isolated myositis presented with higher creatine kinase levels and cardiac involvement (83%), whereas systemic sclerosis-overlap patients often had interstitial lung disease (57%). Histopathology showed a wide spectrum from mild to pronounced myositis with diffuse sarcolemmal MHC-class I (100%) and -II (69%) immunoreactivity, myofiber necrosis (88%), endomysial inflammation (85%), thickened capillaries (84%), and vacuoles (60%). Conspicuous sarcoplasmic protein aggregates were p62, BAG3, myotilin, or immunoproteasomal beta5i-positive. Proteomic and transcriptomic analysis identified prominent up-regulation of autophagy, proteasome, and hnRNP-related cell stress. To conclude, Ku + myositis is morphologically characterized by myofiber necrosis, MHC-class I and II positivity, variable endomysial inflammation, and distinct protein aggregation varying from IBM and IMNM, and it can be placed in the spectrum of scleromyositis and overlap myositis. It features characteristic sarcoplasmic protein aggregation on an acquired basis being functionally associated with altered chaperone, proteasome, and autophagy function indicating that Ku + myositis exhibit aspects of an acquired inflammatory protein-aggregate myopathy.

A Clinical Picture of Unselected Patients with Systemic Lupus Erythematosus in a Tertiary Hungarian Center-A Spectrum Ranging from Pure Lupus to Overlap Syndromes.

Introduction: Systemic lupus erythematosus (SLE) is a multidimensional disease; however, the association of another systemic autoimmune disease further complicates its clinical presentation. Aim: We decided to investigate whether the association of overlap syndromes is linked with a different clinical picture compared to pure lupus and whether this association changes the sensitivity of the following commonly used criteria: the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR), the ACR-1997 and the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. Method: We performed a retrospective observational study among 382 patients afflicted with lupus: we measured as much of the full clinical and laboratory picture as possible in an unselected cohort. The diagnosis of SLE and other systemic autoimmune diseases was established by the rheumatologist in routine care and then the authors compared the characteristics of patients with pure lupus and those with overlapping pathologies. The diagnosis rates were compared to those that were determined based on the three classification criteria in order to identify various sensitivities and whether the existence of an overlap affects their rates. The fulfillment of each set of criteria was calculated using an Excel-based automatic calculation. Results: Among the patients, the ACR 1997's sensitivity was 81.2% (310 patients), and the SLICC 2012 criteria achieved 94.5% sensitivity (361 patients). The 2019 EULAR/ACR classification criteria resulted in a slightly lower sensitivity (90.3%-345 patients) when compared to the original publication (96%) due to the lower sensitivity of our anti-nuclear antibody (ANA) test (measured via enzyme-linked immunosorbent assay (ELISA)). Nearly all ANA-negative (21/22-95%) patients showed a positive lupus-associated antibody test. The proportion of ANA-negative cases showed no significant difference among pure and overlap patients. No significant difference was found between patients with overlap (138 patients-36%) and pure SLE (244 patients-64%) through the use of these criteria, with the exception of the SLICC criteria (ACR: 80.4% vs. 81.6%; SLICC: 97.4% vs. 92.6%, p = 0.035; EULAR/ACR 2019: 91.4% vs. 89.6%). Patients with an overlap syndrome were significantly older (55 vs. 50 years, p = 0.001), more likely to suffer from interstitial lung disease (ILD: 20% vs. 11%, p = 0.0343) and less frequently showed class III/IV lupus nephritis (7% vs. 14%, p = 0.029) when compared with their pure lupus counterparts. Conclusion: All investigated criteria regarding sensitivity were similar to the original publication's findings. The sensitivity of the EULAR/ACR 2019 classification criterion in cases with overlap syndrome proved excellent, with results very similar to patients afflicted with pure SLE. In the presence of an overlap syndrome, we found significantly fewer patients with lupus nephritis III/IV but no differences in other typical lupus organ manifestation beyond the kidney, whereas we found a higher proportion of ILD in patients with an overlap, indicating that the presence of an overlap syndrome significantly influences the observed clinical picture in real-world conditions.