Yao Syndrome: An Overview of Genotypic Associations, Clinical Manifestations, Diagnosis, and Treatment.

BACKGROUND: Yao syndrome (YAOS) is a rare systemic autoinflammatory disorder (AID) of the innate immune system. It was recently categorized as genetically transitional disease (GTD) and is associated with NOD2 variants located at multiple NOD2 gene loci. Unlike most other periodic fever syndromes, the estimated disease prevalence is 1-10/100,000 with a predominance for females and white adult population. In this review, we aimed to provide a detailed analysis of different aspects of this syndrome to help better understand the underlying pathogenesis and incorporate the current evidence-based medicine published to diagnose and manage these patients. SUMMARY: We conducted literature search on YAOS from 2011 to 2024 using PubMed, Embase, and Scopus databases. Thirty-two studies were included in our narrative review. A descriptive analysis was performed of both Yao and non-Yao authored records to embrace the syndrome reported from all investigators and assess differences and similarities. The most reported gene variant is the homozygous IVS8+158 followed by compound heterozygous IVS8+158 and R702W. Mean age of disease onset is between 36 and 42 years. The mean age of disease diagnosis is between 40 and 45 years with a variable disease duration. Fever is the most commonly reported symptom followed by musculoskeletal, gastrointestinal symptoms and dermatitis. On laboratory workup, patients have elevated levels of erythrocyte sedimentation rate, C-reactive protein, and serum ferritin with negative autoantibody workup. Arthritic symptoms in YAOS patients have a positive response to sulfasalazine and glucocorticoids, while nonsteroidal anti-inflammatory drugs and colchicine produce minimal response. Anti-IL1 and anti-IL6 agents (canakinumab, anakinra, and tocilizumab) are effective treatment modalities. KEY MESSAGES: The evolving concept and acceptance of GTD will hopefully further our understanding about this SAID and similar disorders. We suggest developing a registry of patients with YAOS to keep track of expanding data on this subject. It is important to understand various aspects of YAOS including genetic and environmental factors, differential diagnosis, clinical manifestations, laboratory findings, and treatment options available to diagnose and manage these patients appropriately and timely.

Atrial Myxoma: Presenting as a Large Splenic Infarction.

Cardiac myxomas are the most common benign primary heart tumors, with the majority occurring in the left atrium. Clinical manifestations are a result of constitutional, obstructive, and/or embolic events. Complications include myocardial infarction and stroke, as well as renal and limb ischemia. Our unusual case is a middle-aged female who presented with a one-week history of progressively worsening abdominal pain and was found to have a large splenic infarction on a CT scan. There was no personal or family history of autoimmune diseases or hypercoagulable states. The evaluation revealed a large left atrial myxoma confirmed on biopsy after surgical resection. Our patient's clinical presentation was relatively benign compared to the size of her mass. Although her myxoma was very large, morphologically solid, and attached to the interatrial septum, she did not have any evidence of congestive heart failure. The tumor's irregular surface and mobility likely led to splenic embolization. Hence, the differential diagnosis of splenic infarction should include left atrial myxoma.

Cardiac Papillary Fibroelastoma: Atypical Presentation Mimicking Infective Endocarditis With False Positive Commensal Blood Cultures.

Cardiac papillary fibroelastomas (CPFs) are rare benign cardiac neoplasms that carry a high risk of embolization if not diagnosed and managed in a timely manner. As most patients are asymptomatic, CPF may be incidentally detected on transthoracic echocardiography (TTE) when performed for other indications. Management of incidental CPF in asymptomatic patients is debatable. We report an unusual case of an incidental CPF in an asymptomatic patient admitted to the hospital for presumed infective endocarditis (IE). Two weeks following laser resection of laryngeal cancer (LC), a new pansystolic murmur was audible during a routine cardiology visit. Outpatient TTE revealed a "vegetation-like" lesion on the mitral valve (MV). Blood cultures (BC) with Gram-positive cocci in clusters (GPC) were reported within 24 hours. This prompted hospital admission for empiric antibiotics. A transesophageal echocardiogram (TEE) confirmed the lesion to be an echogenic mass attached to the MV consistent with CPF. Repeat BC, prior to empiric antibiotic initiation, were all negative. In the absence of all other signs and symptoms of IE, it was determined that the initial BC was false positive and IE was ruled out. Surgical resection was performed due to the potential risk of embolization. The pathology confirmed the diagnosis of CPF with negative tissue cultures.

Septic Shock From Pan-Spinal Epidural Abscess Attributed to Recent Acupuncture and Trigger Point Injections for Acute Lower Back Pain in a Previously Undiagnosed Diabetic Patient: A Case Report.

Epidural abscesses can lead to devastating neurological consequences if not diagnosed and managed in a timely manner, especially in immunocompromised patients. We report the case of a 60-year-old woman with undiagnosed diabetes mellitus who presented to the hospital with a complaint of progressive altered mental status for the past two days. Eight days prior to presentation, the patient tripped over a pillow at home and developed mildly nagging, acute lower back pain. Upon the recommendation of her friends, she underwent two sessions of acupuncture around the lumbar area on days six and five prior to being brought to the hospital. She also saw her primary care physician on day three prior to presentation, who performed a history and physical examination and, after feeling that she did not have any red flags, empirically administered lidocaine-based trigger point injections near the same lumbar areas with the patient's consent. On the day of presentation, the patient fell at home and was unable to walk, after which she was immediately brought to the hospital, where she demonstrated toxic metabolic encephalopathy due to diabetic ketoacidosis (DKA) and lower extremity paraplegia. Emergent imaging revealed a pan-spinal epidural abscess (PSEA) after an attempted lumbar puncture led to immediate pus in the syringe. Diagnosing an epidural abscess can be difficult as signs and symptoms can mimic other conditions such as meningitis, encephalitis, and stroke. High suspicion on the physician's end is needed when a patient presents with acute back pain, fevers, and neurological deterioration if the condition is otherwise unexplained, and especially in the presence of risk factors for PSEA that may be recognized only upon presentation.

Inpatient Rheumatology Consultation Prompted by Positive Autoantibodies in Patients Receiving Intravenous Immunoglobulin Therapy: A Case Series and Literature Review.

Intravenous immunoglobulin (IVIG) is a therapeutic preparation used in the treatment of multiple diseases. Autoimmune testing with antinuclear antibody (ANA) screening is often obtained for some of these conditions, but only after initiation of IVIG treatment. This can present a diagnostic dilemma in hospitalized patients and may trigger a rheumatology consultation. We describe our consultative inpatient two-year experience with five such patients and review the pertinent literature. A retrospective chart review of rheumatology inpatient consultations between 6-2018 and 6-2020 at our academic tertiary care hospital for post-IVIG positive serologies was performed. A pertinent literature review was performed. Five patients had a positive ANA and other autoantibodies detected in their serum after they received IVIG for non-rheumatological conditions. None of these patients met the criteria for a connective tissue disease. The literature review identified a total of 58 patients from case reports and case series, several of whom tested positive for ANA and other antibodies after receiving IVIG. Studies assessing specific IVIG products detected multiple autoantibodies in the donor pool. Autoimmune testing is initiated on inpatients receiving IVIG for non-rheumatological conditions. If an autoantibody ANA screen is positive, a rheumatology consultation may be requested. In the absence of pre-IVIG antibody tests it is difficult to interpret post-IVIG-positive antibodies. Whether such positive antibodies are of clinicopathological significance is determined by clinical judgment and time.

A Case Report of Anti-phospholipid Syndrome With Lower Extremity Arterial Thrombosis That Didn't Respond to Heparin and Direct Oral Anticoagulation: Ultimately, the Patient Agreed to Oral Warfarin.

In the absence of known thrombophilia or factors associated with thrombotic tendency, clinicians are more likely to think of antiphospholipid syndrome in patients presenting with venous thrombosis than in those with arterial thrombosis. We present a case of acute lower extremity arterial ischemia in a female smoker. Despite multiple surgical interventions and treatment with several different anticoagulants, our patient developed bilateral lower extremity thrombi. Ultimately, after developing a pulmonary embolism, she accepted to be on warfarin. She switched to warfarin without recurrence of her arterial thrombosis. We describe the challenging management of her critical limb ischemia and review the pertinent literature on the controversy surrounding optimal anticoagulation in such patients.

Conversations With Individuals on the Fence about CV-19 Vaccination: Analysis of Lives Saved by Vaccine vs. Natural Infection Mortality and Other Reflections.

As of June 15, 2021, from 672,000 to 912,000 deaths have been averted through vaccination of 48% of the US population. Because 52% remain unvaccinated, 728,000 to 988,000 lives remain at risk. These deaths can be spared, and the pandemic stopped in its tracks provided a final national vaccination rate of 84% is achieved. We aim to demonstrate in our analysis the number of lives saved that can be attributed to CV-19 vaccination vs the mortality rate of natural infection seen in unvaccinated individuals. However, time is short given the recent exponential rise of the highly contagious SARS-CoV-2 Delta variant. Delta infection results in a thousand-fold increase in viral load and a transmissibility 2.25x that of the original SARS-CoV-2 strain. Predominance of the Delta variant has already resulted in Covid-19 surges in area with low vaccination rates. An aggressive and timely vaccination campaign is being attempted. We hope our analysis helps convince individuals 'on the fence' that vaccination is essential if the pandemic is to be ended in the United States.

Posterior Reversible Encephalopathy Syndrome Onset Within 24 Hours Following Moderna mRNA Booster COVID-19 Vaccination: Vaccine Adverse Event Vs. Hypertension?

We present a case of a female who presented with the acute onset of neurological changes within 24 hours of receiving her third, or booster, dose of the mRNA Moderna (Cambridge, Massachusetts) coronavirus disease 2019 (COVID-19) vaccination. Her clinicoradiological findings were most consistent with posterior reversible encephalopathy syndrome (PRES). Although PRES has been reported with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, this raised suspicion of a possible vaccine-induced PRES with her only confounder being hypertension managed with a beta-blocker. Extensive workup for other entities associated with PRES, including infection, autoimmune, paraneoplastic syndrome, and alcohol were unrevealing. Thus far, there have not been any reports of PRES post mRNA vaccination. We encourage providers to report similar cases with neurological manifestations post mRNA vaccination to the vaccine adverse event reporting system (VAERS). Timely diagnosis and treatment of PRES may help minimize any irreversible neurological sequelae.

Diagnosing and Managing Clinically Silent Lupus Nephritis and Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome: A Clinical Challange.

Lupus nephritis is typically associated with anti-nuclear antibodies and anti-double-stranded DNA antibodies resulting in the intrarenal immune complex deposition. Levels of anti-double-stranded DNA antibodies reflect disease activity in these patients. With negative anti-double-stranded DNA antibodies, establishing a diagnosis of lupus nephritis is difficult. Lupus nephritis overlapped with anti-neutrophil cytoplasmic antibody-associated vasculitis is both a diagnostic and therapeutic dilemma. Herein, we describe a case of an asymptomatic 41-year-old female who had incidental findings of low hemoglobin and elevated serum creatinine. Making a clinical diagnosis of lupus nephritis and anti-neutrophil cytoplasmic antibody-associated vasculitis in an asymptomatic patient can be challenging and must be made based on the interpretation of evolving serology, imaging studies, and histopathology. Based on extensive workup, the patient was diagnosed with concurrent lupus nephritis and anti-neutrophil cytoplasmic antibody-associated vasculitis overlap syndrome warranting immediate immunosuppressive therapy.

A Patient's Six-Month Journey From Low Sodium to Blue Toes to Stroke: Non-infective Thrombotic Endocarditis Due to Non-small Cell Lung Cancer.

We report a patient's journey with a four-year history of hypertension (HTN) and hyperlipidemia (HLD), stable on beta-blocker and statin, monitored every six months by alternating visits between her cardiologist and primary care physician (PCP) in North Carolina (NC). Six months before relocating to New York (NY) she had been informed about incidental severe hyponatremia during her last outpatient visit, the need for repletion with sodium chloride tablets, and the critical importance of prompt follow-up to rule out malignancy by starting with a chest X-ray. She opted not to follow instructions, continued cigarettes, and decided to spend the summer season with her son in NY. Six months after being told of her low sodium, she presented to our NY hospital with an acute, painful right foot blue toe syndrome. During the ischemic right foot evaluation, she was discovered to have adenocarcinoma of the right lung (stage 4) and a normal transthoracic echocardiogram (TTE). Heparin was initiated and thromboembolectomy with an endovascular bovine patch to revascularize the foot was successful, and post-procedure apixaban was started. Hyponatremia was attributed to the syndrome of inappropriate antidiuretic hormone release (SIADH) secondary to non-small cell lung cancer (NSCLC). The serum sodium was stabilized, and the patient was discharged with a plan for outpatient follow-up with the cardiologist and oncologist within two weeks for hypertension, hyperlipidemia, hyponatremia, and management of stage 4 NSCLC. During her cardiology follow-up, 10 days after discharge, complaints of mild dyspnea on exertion (DOE) prompted an ECG (electrocardiogram) that revealed new T wave inversions in leads V3-6, and the patient was readmitted for non-ST elevation myocardial infarction (NSTEMI) evaluation. On day one of the readmission troponins were negative with normal ejection fraction (EF) on TTE and an acute 2 g/dl hemoglobin (Hb) drop with melena. This led to discontinuation of anticoagulation, initiation of intravenous (IV) pantoprazole, and endoscopy (EGD) which revealed gastritis. On the third day, she developed sudden expressive aphasia. Computed tomography (CT) of the head did not show any bleed but same-day magnetic resonance imaging (MRI) demonstrated multiple evolving acute infarcts. Transesophageal echocardiogram (TEE) demonstrated two large, mobile masses on the mitral valve consistent with vegetative endocarditis. Cultures for bacteria, fungi, and evaluation for organisms associated with culture-negative acute bacterial endocarditis/subacute bacterial endocarditis were unrevealing, thus confirming malignancy-associated non-infectious thrombotic endocarditis or non-bacterial thrombotic endocarditis (NBTE). Gastrointestinal (GI) bleeding ceased, and the patient initially started on a heparin drip and transitioned to enoxaparin as lifelong anticoagulation for malignancy-associated NBTE. She recovered neurologically and was given pembrolizumab. At her recent 15-month visit she continued to have no residual neurological impairments, however, new positron emission tomography (PET) detected metastasis to the liver, lung, and adrenals which prompted evaluation for hospice care. We, therefore, emphasize the need for timely diagnosis of NBTE and prompt initiation of anticoagulation in suitable patients to prevent complications such as in our patient. Additionally, hyponatremia secondary to SIADH in NSCLC is a poor prognostic indicator of overall survival.