Overlap Syndrome Research Articles

Insights into the Overlap of Chronic Obstructive Pulmonary Disease and Sleep Apnea: Experience from the Clinic of Pneumology, Târgu Mureș

Introduction: Chronic obstructive pulmonary disease (COPD) has a severe impact on patients’ health and can lead to multiple complications. Material and methods: We analyzed the co-occurrence of obstructive sleep apnea (OSA) in COPD patients hospitalized in the Pneumology Clinic of Târgu Mureș, Romania. Results: A total of 150 COPD patients were investigated by clinical examination, STOP-BANG and Epworth questionnaires, ventilatory polygraphy (PG), EKG, cardiac ultrasound, blood lipids, and sugar. Sixty-eight patients (45.3%) had OSA associated with COPD. A total of 61.7% were COPD gr. E, and 30.8% were gr. B. Frequently shown symptoms were snoring and nonrestorative sleep (100%), somnolence (73.5%), nocturnal awakenings (41.17%), morning headache (32.3%), and aggravated dyspnea. Types of OSA included obstructive (97.05%), central (2.5%), and associated obesity–hypoventilation (39.7%). A total of 76.4% were recently diagnosed with OSA. Men predominated at 70.5%, 76.4% were smokers, and 61.7% had experienced alcohol abuse. A total of 25% were overweight, and 71% had obesity. A total of 13.2% belonged to the category of 38–50-year-olds, 55.8% were in the 51–65-year-old category, 17.6% were in the 66–70-year-old category, and roughly 13.2% were in the 71-year-old category. Overlap syndrome (OS) comorbidities and complications were frequently present: 41% experienced respiratory failure, 66.1% experienced blood hypertension, 58.8% experienced ischemic cardiac disease, 32.35% experienced diabetes mellitus, 50% experienced dyslipidemia, and 29.4% experienced cor pulmonale. Conclusions: OS conferred gravity or directly contributed to cardiovascular, respiratory, and metabolic complications. OS was associated with more severe COPD and obesity. The prevalence of smoking in OS patients was higher than the national/European average.

A novel m.5906G > a variant in MT-CO1 causes MELAS/Leigh overlap syndrome.

The MELAS/Leigh overlap syndrome manifests with a blend of clinical and radiographic traits from both MELAS and LS. However, the association of MELAS/Leigh overlap syndrome with MT-CO1 gene variants has not been previously reported. In this study, we report a patient diagnosed with MELAS/Leigh overlap syndrome harboring the m.5906G > A variant in MT-CO1, with biochemical evidence supporting the pathogenicity of the variant. The variant m.5906G > A that led to a synonymous variant in the start codon of MT-CO1 was filtered as the candidate disease-causing variant of the patient. Patient-derived fibroblasts were used to generate a series of monoclonal cells carrying different m.5906G > A variant loads for further functional assays. The oxygen consumption rate, ATP production, mitochondrial membrane potential and lactate assay indicated an impairment of cellular bioenergetics due to the m.5906G > A variant. Blue native PAGE analysis revealed that the m.5906G > A variant caused a deficiency in the content of mitochondrial oxidative phosphorylation complexes. Furthermore, molecular biology assays performed for the pathogenesis, mtDNA copy number, mtDNA-encoded subunits, and recovery capacity of mtDNA were all deficient due to the m.5906G > A variant, which might be caused by mtDNA replication deficiency. Overall, our findings demonstrated the pathogenicity of m.5906G > A variant and proposed a potential pathogenic mechanism, thereby expanding the genetic spectrum of MELAS/Leigh overlap syndrome.

Anti-SRP Antibodies and Myocarditis in Systemic Sclerosis Overlap Syndrome with Immune-Mediated Necrotizing Myositis (IMNM)

Overlap syndrome of systemic sclerosis and idiopathic inflammatory myopathies is an increasingly frequent entity, but the association with immune-mediated necrotizing myositis has rarely been described. While myositis or myopathy may be features of scleroderma, it is imperative to correctly diagnose an overlap syndrome of these two, since it can be considered a different entity with specific management and a worse prognosis. Anti-signal recognition particle (anti-SRP) antibodies target the striated muscle fiber and inhibit myoblast regeneration, resulting in myofiber atrophy and necrosis. Anti-SRP antibodies are specific in immune-mediated necrotizing myopathy characterized by myonecrosis and minimal inflammatory reaction, with proximal muscle weakness and typical extra-muscular manifestation. There are controversial data on the association of cardiac manifestations and the presence of these antibodies, and recent studies cannot prove a significant correlation between the two. Myocarditis is a complication with an unpredictable, potentially severe outcome from heart failure and dilated cardiomyopathy to fatality. It can be difficult to diagnose, and a myocardial biopsy can be problematic in daily practice; thus, most practitioners rely on cardiac magnetic resonance with suggestive images for the correct diagnosis. This paper seeks to address the challenges associated with the diagnosis and treatment of collagen diseases by evaluating the role of anti-SRP antibodies in the pathogenesis of cardiac involvement.

Long-term mortality in patients with chronic obstructive pulmonary disease requiring acute non-invasive ventilation with and without obstructive sleep apnoea

IntroductionChronic obstructive pulmonary disease (COPD)/obstructive sleep apnoea (OSA) overlap syndrome (OVS) is associated with higher mortality compared with COPD alone in stable outpatients. However, the prognosis of patients hospitalised with...

Pharmacological Correction of Gastrointestinal Motility in Patients with Functional Gastrointestinal Disorders

Actuality. Functional gastrointestinal disorders (FGID) represent a significant public public health issue. The foundation of effective therapy for FGID with overlap syndrome - functional dyspepsia (FD, epigastric pain syndrome) with gastric hypersecretion and irritable bowel syndrome (IBS)-is considered to be pathogenetic therapy or the combined use of symptomatic medications. Aim. Assessment of the impact of pathophysiological therapy with the drug Kolofort and symptomatic treatments, including proton pump inhibitors (PPIs) and the myotropic antispasmodic mebeverine hydrochloride in prolonged-release capsules, on the clinical manifestations of FGIDs with overlap syndrome - FD (pain syndrome in the epigastric region) with gastric hypersecretion and IBS - includes evaluating effects on myoelectric activity of the gastrointestinal tract. Design. (conception) An open cohort-controlled comparative study on the effects of Kolofort, omeprazole, rabeprazole, and mebeverine hydrochloride in prolonged-release capsules on intestinal motility in patients with FGID and overlap syndrome - functional dyspepsia (FD, epigastric pain syndrome) with gastric hypersecretion and IBS. Materials and Methods. A total of 107 patients suffering from FGID with overlap syndrome - functional dyspepsia (FD, epigastric pain syndrome) with gastric hypersecretion and IBS - were examined. Results. A one-month course of Kolofort significantly improved the psychological status of IBS patients and enhanced intestinal myoelectric activity. Since there is no available literature on Kolofort’s effect on gastric secretion levels, PPIs and mebeverine hydrochloride were used in the treatment of patients with FGID - FD (epigastric pain syndrome) with gastric hypersecretion and IBS overlap syndrome. The use of PPIs, such as omeprazole and rabeprazole, in these patients eliminated gastric hypersecretion and abdominal pain. Rabeprazole demonstrated faster effects than omeprazole and also normalized gastrointestinal motility more efficiently. For patients with FGIDs - FD with gastric hypersecretion and overlap syndrome with IBS, a combined therapy of omeprazole and the myotropic antispasmodic mebeverine hydrochloride in prolonged-release capsules is recommended. This combination, within two weeks, resolved clinical symptoms in 97% of cases, improved the quality of life, and normalized intestinal motility and gastrointestinal myoelectric activity. However, monotherapy with rabeprazole at a daily dose of 20 mg more rapidly addressed symptoms of gastric hypersecretion and and normalized gastrointestinal motility.

Overlap syndrome in liver diseases in children: case report and literature review

In children, autoimmune liver diseases can manifest in a variety of forms, including autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and the co-occurrence of AIH and PSC - the “overlap syndrome.” Early recognition of overlap syndrome is important. Diagnosis of sclerosing cholangitis largely depends on the cholangiographic picture showing single or multiple strictures with dilatation of the biliary tract. The problems of etiology, pathogenesis, diagnosis and treatment of overlap syndrome in children are shown. A clinical example of seronegative autoimmune hepatitis and sclerosing cholangitis as part of a cross syndrome in a child is given.

Clinical characteristics of children with MT-TK gene m.8344A>G variation

Objective: To summarize the clinical characteristics of children carrying the m.8344A>G variant of MT-TK gene. Methods: A case series study was conducted to retrospectively collect data of 22 children with mitochondrial disease caused by MT-TK gene m.8344A>G variation who were treated at the Department of Neurology of Beijing Children's Hospital of Capital Medical University from January 2012 to January 2024. Their clinical data, laboratory tests, muscle pathology, genetic testing, and the follow-up results were analyzed. Pearson correlation analysis was used for correlation analysis. Results: Among the 22 children, there were 13 boys and 9 girls. The age of onset was 5.00 (2.75, 9.00) years. Fifteen children had myoclonic epilepsy with ragged-red fibers (MERRF), 3 had Leigh syndrome (LS), and 4 had LS-MERRF overlap syndrome (LS-MERRF). Myoclonus presented and worsened progressively in all 15 MERRF children, with 10 as the initial symptom and 5 developing progressively during the disease course. Myoclonus was predominantly focal, worsening with fine motor tasks or stress. Electroencephalogram monitoring in the 15 MERRF children revealed myoclonic seizures in 10 children, with 6 classified as myoclonic epilepsy, and 4 as subcortical myoclonus. Two children had generalized myoclonic seizures, and 1 each had absence seizures and generalized seizures. Twelve children had cerebellar ataxia, 10 children exhibited exercise intolerance, and 8 children had muscle weakness. Magnetic resonance imaging (MRI) revealed periventricular white matter involvement in 1 child and bilateral hippocampal involvement in 1 child, likely due to frequent seizures. All 3 children with LS exhibited developmental regressions, accompanied with 2 symptoms include cerebellar ataxia, muscle weakness, and dysphagia. The clinical manifestations of 4 LS-MERRF overlap children presented with combined features of MERRF and LS. Cranial MRI in the 7 LS and LS-MERRF children showed brainstem involvement (all affecting the midbrain) in 6 children and basal ganglia involvement in 4 children. Among the 22 children, 12 had m.8344A>G variant levels >90%, 3 had >80%-90%, 4 had >70%-80%, and 3 had >60%-70%. Higher variant level correlated with the LS phenotype and earlier onset age (r=0.47, -0.50; P=0.018 and 0.029, respectively). Sanger sequencing in 19 mothers revealed m.8344A>G variations in 18, with 4 showing exercise intolerance. Follow-up of 13 children on antimyoclonic treatment showed>75% reduction in seizures with levetiracetam monotherapy in 2 children, with combination therapy required in others. Most achieved >50% seizures reduction within 2 years, but the effectiveness declined with disease progression. Conclusions: The m.8344A>G variant is rare, with MERRF being the most common phenotype, while LS and LS-MERRF are less common. Children with higher ratio of the m.8344A>G variant are more likely to present LS phenotype. Myoclonus, primarily focal, is a key feature, with levetiracetam as the first-line treatment and benzodiazepines recommended for refractory cases.

The Impact of Lung Function on Sleep Monitoring in Obstructive Sleep Apnea Associated with Obstructive Lung Diseases: Insights from a Clinical Study.

Background/Objectives: Obstructive sleep apnea (OSA) and obstructive lung diseases (OLD) are common and interdependent respiratory disorders, where one condition may contribute to the development and worsening of the other (OLDOSA syndrome). The term OLDOSA syndrome includes two different conditions: Overlap syndrome (OVS: OSA + chronic obstructive pulmonary disease, COPD) and Alternative Overlap syndrome (aOVS: OSA + Asthma). Data on the interactions between lung function and respiratory monitoring during sleep in OLDOSA patients are few and controversial. Our study aims to evaluate the impact of lung function impairment on sleep breathing disorders, paying attention to the lack of literature about comparisons between OVS, aOVS, and the impact of small airways disease (SAD) in these patients. Methods: In total, 101 patients with a diagnosis of OSA and asthma or COPD underwent pulmonary function tests (PFTs) and nocturnal home sleep cardiorespiratory monitoring (HSCM). Exclusion criteria: Obesity hypoventilation syndrome (OHS) and other non-respiratory sleep disorders. Results: Sleep time with oxygen saturation below 90% (T90) was negatively correlated with forced expiratory volume in the first second, % of predicted (%FEV1), forced vital capacity, % of predicted (%FVC), forced expiratory flow at 25-75% of the pulmonary volume, % of predicted (%FEF25-75), and, after multivariable linear regression analysis, %FEF25-75 remained an independent factor for T90 with a negative correlation in mild and moderate OSA. Obstructive apnea index (oAI) and FEV1/FVC were negatively correlated in mild and moderate OSA. OVS presented with more severe OSA (higher AHI, oAI, and T90) and SAD (lower FEF25-75) compared to aOVS. Conclusions: This study highlights a possible interdependence between OLD and OSA; obstruction of the large and small airways at PFTs contributes to the worsening of these patients' nocturnal hypoxemia and obstructive events of the upper airway during sleep. Furthermore, this study shows that patients with OVS should be carefully monitored, as they present worse data at HSCM and have greater small airways involvement compared to aOVS.

Frequency of detection of dyssynergic defecation in patients with overlap syndrome of functional disorders of the digestive organs associated with constipation

Introduction. The presence of dyssynergic defecation in a cohort of patients with overlap syndrome of functional disorders is poorly studied.Aim. To assess the motor function and sensitivity parameters of the anorectal zone, to identify dyssynergic defecation and to analyze the frequency of correlation in patients with overlap syndrome of functional gastrointestinal disorders associated with constipation.Materials and methods. A one-stage examination was conducted in four parallel groups. The study included 100 patients aged 30 to 40 years with the following diagnoses: constipation-p redominance irritable bowel syndrome (IBS-C) (group 1), IBS-C combined with functional dyspepsia (group 2), IBS-C combined with functional biliary disorder (group 3) and healthy volunteers (group 0). All patients underwent a balloon expulsion test and high-resolution anorectal manometry to determine the presence of dyssynergic defecation.Results. Based on the analysis of parameters according to anorectal manometry data, dyssynergic defecation was not detected in group 0, in group 1 dyssynergic defecation was detected in 8 people – 32.0% (95% CI 12.3–51.6), in group 2 – in 14 people – 56.0% (95% CI 35.0–76.9), in group 3 – in 16 people – 64.0% (95% CI 43.7–84.2). A negative evacuation test was detected in 8 (32%) patients in group 1, in 14 (56%) patients in group 2, and in 17 (68%) patients in group 3, which confirmed the presence of dyssynergic defecation.Conclusions. This study demonstrated the presence of dyssynergic defecation in three groups of subjects, more often with a combination of irritable bowel syndrome with predominant constipation with functional dyspepsia, and most often with a functional disorder of the gallbladder.

Diagnostic Challenge of Lupus with Overlap Syndrome in an Adolescent: A Case Report

Lupus with overlap syndrome is an uncommon autoimmune disease that typically affects teenage females. It can present as various symptoms affecting multiple organs. Delay in the diagnosis of lupus will lead to deleterious effects on the implicated adolescents’ health. The case report aims to describe the diagnostic challenge of a refractory skin disease leading to a delay in diagnosis and highlight its psychosocial impact. Here, we describe a case of a teenager who presented with poorly controlled chronic dermatitis. The chronic dermatitis was refractory to the first-line therapy of topical steroids and emollients. She was finally diagnosed with lupus and overlap syndrome, confirmed by a skin biopsy. In conclusion, any chronic refractory skin diseases warrant further referral and investigation at the tertiary centre. Assessment of psychosocial in managing chronic skin disease in adolescent is essential as it could implicate their mental health further.

A Case of Neuromyelitis Optica Spectrum Disorder/Systemic Lupus Erythematosus Overlap Syndrome Initially Misdiagnosed as Bacterial Meningitis

A Case of Neuromyelitis Optica Spectrum Disorder/Systemic Lupus Erythematosus Overlap Syndrome Initially Misdiagnosed as Bacterial Meningitis

Immune Checkpoint Inhibitor Related Myositis/Myasthenia Gravis Overlap Syndrome Treated with Eculizumab

Immune Checkpoint Inhibitor Related Myositis/Myasthenia Gravis Overlap Syndrome Treated with Eculizumab

12431 14-year-old Presenting With Thrombocytopenia-Associated Multi-Organ Failure In The Setting Of Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome

Abstract Disclosure: N.C. Gunaratne-Breaux: None. D. Deplewski: None. Title: 14-Year-Old Presenting with Thrombocytopenia Associated Multi-Organ Failure in the setting of Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome Background: Coagulation complications are rare in hyperglycemia emergencies in children and adolescents. In patients presenting with severe and atypical hyperglycemia emergencies, special considerations need to be made to rule out life-threatening coagulopathy. Clinical Case: A 14-year-old male with history of Type 1 Diabetes presented in severe Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome overlap. Initially had severe hypotension and altered mental status concerning for cerebral edema. Initial venous blood gas showed pH of 6.82, pCO2 17.1, and HCO3 2.8, serum glucose was 1375 mg/dL, serum ketones >7.00 mmol/L, and serum osmolality was 384 mOsm/kg. Once insulin drip was started, glucose, ketones, and serum osmolality improved, but patient continued to be encephalopathic and had worsening tachypnea and desaturations. Patient was eventually intubated. After intubation, patient’s acidosis improved, but patient developed kidney failure (prompting initiation of dialysis), liver injury, decreased cardiac function, and high inflammatory state. A comprehensive multi-specialty team including pediatric intensive care, infectious diseases, rheumatology, neurology, and cardiology were involved in the care. On day three of admission, patient had multiple areas of ischemia on fingertips and ear and clotting of multiple IV and dialysis catheters, prompting a coagulopathy evaluation. Labs showed microcytic anemia (hemoglobin 10.0 g/dL; mean corpuscular volume 75fL), thrombocytopenia (platelet count 17 10e3/uL), coagulopathy (prothrombin time 16.8 sec, INR 1.3, prolonged thrombin time 48.8 sec), and elevated ferritin (507 ng/mL). Given labs and multi-organ involvement, determined by hematology to be Thrombocytopenia Associated Multi-Organ Failure (TAMOF). Patient was started on plasmapheresis and had dramatic improvement – was eventually extubated and returned to neurologic baseline without any notable deficits. Multi-specialty team ruled out all other possible causes of TAMOF; determination that the TAMOF developed secondary to DKA/HHS. Conclusion: Hyperglycemia emergencies can lead to a hyperinflammatory state that can lead to disruption of the coagulation cascade, including disseminated intravascular coagulopathy or thrombotic thrombocytopenia purpura. There have been rare reports of thrombocytopenia associated multi-organ failure provoked by DKA, thought secondary to critical illness mediated low ADAMST13 levels. This is a novel case of TAMOF caused by DKA/HHS overlap syndrome. It is important to screen for coagulopathy in cases of patients with DKA or DKA/HHS who do not show clinical improvement with resolution of ketosis and hyperosmolarity. Presentation: 6/2/2024

Overlap syndromes in sarcoidosis: Unveiling the masquerader

As a multi system granulomatous disease, clinical presentations of sarcoidosis are highly variable. In the absence of a stereotypical clinical presentation such as asymptomatic bilateral hilar adenopathy, Lofgren's syndrome, or lupus pernio, a diagnosis of sarcoidosis typically requires 1) compatible clinical presentation, 2) histologic evidence of granulomatous inflammation, and 3) the exclusion of other causes. The clinical presentation of sarcoidosis is often nonspecific and a variety of other causes of granulomatous inflammation can make diagnosing sarcoidosis a challenge for clinicians. “Overlap syndromes” are often used to describe clinical presentations of sarcoidosis that share histologic and clinical features of other diseases, or when the diagnosis of sarcoidosis is made in association with the coexistence of another diagnosis with similar clinical or histologic findings. Because of the risk of diagnostic delay and diagnostic errors, it is vital for clinicians to be familiar with overlap syndromes in sarcoidosis. The coexistence of sarcoidosis with other diseases can also significantly impact disease management and outcomes. This article will review the most current published data on overlap syndromes in sarcoidosis to aid clinicians in diagnosing and managing these complex patients.

549VP High dose intravenous corticosteroids in refractory immune checkpoint inhibitor-related myocarditis/myositis/myasthenia overlap syndrome

549VP High dose intravenous corticosteroids in refractory immune checkpoint inhibitor-related myocarditis/myositis/myasthenia overlap syndrome

Association of Bartter Syndrome in a Filipino Patient with Overlap Syndrome

Association of Bartter Syndrome in a Filipino Patient with Overlap Syndrome

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.

S3996 EUS-Guided Liver Biopsy in Pediatric Cholestasis: A Case Report of PSC/AIH Overlap Syndrome

S3996 EUS-Guided Liver Biopsy in Pediatric Cholestasis: A Case Report of PSC/AIH Overlap Syndrome

Autoimmune Ascites, a Manifestation of an Overlap Syndrome: Diffuse Systemic Sclerosis and Systemic Lupus Erythematosus

Autoimmune Ascites, a Manifestation of an Overlap Syndrome: Diffuse Systemic Sclerosis and Systemic Lupus Erythematosus

A Diagnostic Dilemma of Lupus Nephritis and ANCA-Associated Vasculitis Overlap Syndrome

A Diagnostic Dilemma of Lupus Nephritis and ANCA-Associated Vasculitis Overlap Syndrome