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Patients with bicuspid aortic valve (BAV) experience valvular complications at an accelerated rate. While BAV is generally regarded as a benign anatomical variant, recent histological and cardiac imaging studies suggest significant hemodynamic instability in even asymptomatic BAV patients.

A previously healthy 59-year-old man was referred for new-onset difficult-to-control hypertension. Echocardiography revealed a mildly calcified but well-functioning bicuspid aortic valve (BAV) and there were signs of chronically elevated left-sided heart pressures, though the patient denied any symptoms and exercise stress testing was normal. Over the next 2 years he failed multiple antihypertensive drug regimens despite proper compliance. He eventually presented to the hospital with profound hypotension and was found to have infective endocarditis complicated by a perivalvular abscess requiring mechanical aortic valve replacement (AVR). Prior to AVR, he struggled to maintain blood pressure on a 3-drug regimen and his response to atenolol reflected that of elderly patients with isolated systolic hypertension from age-related aortic stiffening. Following AVR, a dramatic improvement was observed in the patient’s blood pressure, now responsive to nebivolol monotherapy at half the previous dose, and he has remained stable at 1, 3, and 6-month follow up.

Hemodynamic instability and ascending aorta stiffness are obvserved in BAV patients independently of age, valvular function, aortic diameter, or atherosclerotic risk factors. While the exact etiology of aortic stiffening in BAV patients has not been confirmed, recent histological studies suggest a similar–but
accelerated–mechanical stress-induced phenotypic shift in vascular smooth muscle cells (VSMCs) which has previously been implicated in thoracic aortic disease and age-related aortic stiffening. Reactive deposition of extracellular matrix initially serves to dampen mechanical stress and maintain homeostasis; however this ultimately increases pulse wave velocity (PWV) and central systolic pressure, perpetuating a feedforward loop of maladaptive stiffening and increased myocardial demand. Supporting these findings are recent strain imaging studies revealing subclinical diastolic dysfunction associated with aortic stiffness in asymptomatic BAV patients. Consensus guidelines for BAV surveillance currently address aortic aneurysm detection but fail to address its likely precursor–loss of proximal aortic distensibility due to the intrinsic hemodynamic abnormalities of BAVs. Strain imaging offers immense value for this application but is not yet widely available in clinical practice. In the meantime, assessment of PWV on doppler echocardiography may be a valuable surrogate for aortic stiffness in BAV patients.


AMA Research Challenge 2024 

Resolution of Hypertension Following Replacement of a “Well-Functioning”
Bicuspid Aortic Valve: Re-examining Aortic Stiffness in Asymptomatic BAV Patients

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BACKGROUND: Intracranial infected aneurysms (IIAs), also known as mycotic aneurysms, complicate infective endocarditis (IE) in around 2-4% of cases. IIAs can spontaneously rupture and present with intracerebral bleeding, which is usually straightforwardly recognized in brain imaging. This case documents a rare presentation of a ruptured IIA initially misdiagnosed as a brain neoplasm due to clearly suggestive radiologic features.

CASE PRESENTATION: A 43-year-old male with history of cocaine and tobacco consumption and treated tuberculosis was admitted for tonic-clonic seizures and right hemiparesis along with a 3-month history of persistent fever, malaise, and 15-kg weight loss. A head computed tomography (CT) showed a left frontal lesion having both solid and central hemorrhagic content along with surrounding vasogenic edema and intraventricular hemorrhage. In the magnetic resonance imaging, the brain lesion was expansive and showed contrast enhancement. The workup showed elevated inflammatory markers and glomerulonephritis but was otherwise unremarkable for infectious, autoimmune, or oncological etiologies. At present, the primary suspicion was a brain tumor based on the characteristic radiologic features, the otherwise unremarkable workup including negative pan-cultures and transthoracic echocardiogram (TTE), and the maintenance of afebrile status following oral prednisone for vasogenic edema. He was discharged for outpatient follow-up. Around 3 months later, he was readmitted for persistent fever; a new TTE showed mitral valve vegetations and blood cultures grew Streptococcus mutans, confirming IE. A brain CT angiography confirmed multiple IIAs. He received intravenous ceftriaxone and vancomycin. Besides, the hospital course was complicated by decompensated heart failure and myocardial infarction with an obstructive coronary artery that required mitral valve and coronary artery bypass graft surgery, respectively. He was discharged hemodynamically stable.

DISCUSSION: IIAs represent an embolic complication of IE caused by septic arterial emboli that travels to the vasa vasorum of cerebral arteries and triggers a local inflammation and dilation of the arterial wall. Ruptured IIAs present with intracranial hemorrhage in brain imaging studies. However, this case and other around two-to-four cases documented that ruptured IIAs can rarely mimic intra-axial masses, leading to misdiagnosis. For example, similarities between IIAs and glioblastoma multiforme were reported, as both conditions can enhance contrast in imaging. It is unclear if this presentation is extremely rare or is underreported. This case documents a ruptured IIA presenting radiologically as a brain cerebral neoplasm. As a final reminder, clinicians should be aware of this unique presentation to maintain a high index of suspicion for IIAs despite unremarkable blood cultures and echocardiography.

Ruptured Intracranial Infectious Aneurysm (IAAs) Mimicking an Expansive Brain Tumor: Endocarditis Case

Background 
Cardiac myxomas are the most common primary cardiac tumors. They are benign, but considered “functionally malignant” due to high potential for embolization. Transthoracic and Transesophageal echocardiography (TTE/TEE) are the imaging modalities of choice when evaluating for myxoma. Cardiac MRI, CT and PET scan are also useful in establishing a diagnosis. There are few documented cases of cardiac myxomas associated with Atrial Septal Defect (ASD) occluder devices. At present, there is no established relationship between myxoma and ASD occluder devices. Interestingly, cardiac myxomas have been theorized to predispose patients to Takotsubo Cardiomyopathy through CNS and systemic mechanisms.

Case Presentation
A 75 year old female with a past medical history of hypertension, hyperlipidemia, atrial fibrillation, and an atrial septal defect with an ASD occluder device presented to an outside hospital with concerns for an acute cerebrovascular accident (CVA). Stroke workup revealed multiple embolic infarcts. Further evaluation with TTE revealed a normal ejection fraction and a semi-mobile mass in the left atrium, which appeared to be associated with the ASD closure device. During the hospitalization, the patient experienced another rapid decline, which was found to be a new embolic MCA infarct. Repeat TTE confirmed the pre-existing mobile mass and noted a hypokinetic apex with an ejection fraction of 20% concerning for Takotsubo cardiomyopathy. TEE visualized two left atrial mobile masses on the interatrial septum, and confirmed absence of a thrombus. Each mass appeared to be connected by a stalk, a finding highly suspicious of myxomas. MRI reported a well circumscribed, semi-mobile, spherical mass in the left atrium attached to the ASD occluder device and CT scan noted a large filling defect adjacent to the closure device. The patient was not a surgical candidate due to multiple comorbidities. She was kept comfortable and died shortly thereafter. 

Discussion
Thrombi are known to attach to ASD occluder devices. However, there are very few cases of cardiac myxomas doing so. A similar case report hypothesized that enhanced endothelialization after ASD occluder device placement may promote further cell transformation, leading to myxoma. Advanced imaging assists in further characterizing cardiac myxoma; However, there are still challenges in differentiating between myxoma and thrombus. In our case, TEE using real time 3D reconstruction provided the best visualization of the masses. Surgery is required to make a definitive diagnosis. Finally, myxomas may lower the threshold for development of Takotsubo cardiomyopathy, which can impact surgical planning.

Two Presumed Cardiac Myxomas Associated with ASD Occluder Device, and Subsequent Development of Takotsubo Cardiomyopathy: A Case Report

Cardiac tamponade, a critical medical emergency, mandates immediate intervention due to its life-threatening hemodynamic instability. While Coxsackie B virus infrequently leads to cardiac tamponade, documented cases are scarce. Moreover, the simultaneous occurrence
of bilateral pleural effusion adds an unusual dimension to its clinical presentation. Serositis, a hallmark of connective tissue disorders like systemic lupus erythematosus (SLE), is encountered often. Yet its co-presentation with hemorrhagic viral pleural
effusion and cardiac tamponade of this severity remains exceptionally rare. 

A 77-year-old male with a medical history notable for SLE, relapsing polychondritis, and paroxysmal atrial fibrillation, presented with palpitations and dyspnea. Electrocardiography revealed atrial fibrillation with rapid ventricular response, necessitating
immediate cardioversion in the emergency department due to hemodynamic instability. Subsequent chest computed tomography demonstrated moderate pericardial effusion alongside bilateral pleural effusions. Despite initial stabilization, recurrent episodes of
hemodynamic instability ensued. Prompt transthoracic echocardiography confirmed tamponade physiology, prompting urgent pericardiocentesis and thoracentesis with drainage of serosanguinous fluid. Fluid analysis confirmed an exudative nature. Exacerbation of
SLE was ruled out (by normal anti-dsDNA antibodies and complement levels (especially CH50, C3, C4)), while serological testing revealed elevated Coxsackie B1 virus titers (1:80). 

Coxsackie B virus exhibits diverse clinical manifestations, ranging from benign viral prodrome to severe cardiac involvement. Maintaining a high clinical suspicion is crucial to avoid anchoring bias and for timely diagnosis, especially in distinguishing viral-induced
pathology from more conventional causes like SLE. This case underscores the importance of recognizing rare viral etiologies in patients with similar presentations mimicking an exacerbation of underlying autoimmune disorders.

Unveiling Coxsackie B Virus-Induced Cardiac Tamponade with Bilateral Pleural Effusion in a Patient with Systemic Lupus Erythematosus: A Rare Case Report

Lipschütz ulcers (LU), also known as reactive non-sexually related acute genital ulcerations, are an uncommon condition that primarily affects sexually inactive girls under the age of 20 years. In this report, we describe a 13-year-old female with past medical history of periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) in early childhood who presented to the emergency department (ED) for sudden onset of genital ulcerations and labial swelling. Based on her clinical presentation, negative primary infectious workup, unresponsiveness to broad-spectrum antimicrobials, and concurrent viral infection, she was diagnosed with LU. Her simultaneous presentation with aphthous stomatitis was unique and may indicate that PFAPA history potentially influences susceptibility to developing LU.

A case of Lipschütz ulcers in a 13-year-old with PFAPA syndrome

Abstract Title
An Unusual Presentation of Erythrodermic Psoriasis
Background
Erythrodermic psoriasis is a rare form of psoriasis, occurring in less than 3% of patients with psoriasis. Limited information is known regarding diagnosis and treatment for this form of psoriasis, with most studies involving small groups or single patients. This unusual case of erythrodermic psoriasis outlines the presentation, diagnosis, and treatment that occurred in a 53-year-old patient who initially presented with dyspnea and a fever.
Case Presentation
The patient had a history of type 2 diabetes, psoriasis, COPD, atrial fibrillation, peripheral arterial disease, and DVT. Lab work showed evidence of leukocytosis and viral testing was done, which was negative for COVID and RSV. The patient suddenly developed a diffuse rash during the admission. A maculopapular rash developed diffusely on the upper extremities, lower extremities, trunk, and face. The rash then desquamated over the course of several days, appearing as exfoliating and scaling skin. The patient underwent two punch biopsies for diagnosis. She was treated with Hydrocortisone (2.5%) cream for the face and inguinal regions and Triamcinolone for the trunk. The patient continued this regimen daily for 2 weeks, and then alternated days for the following 2 weeks, and then stopped.
Discussion
Erythrodermic psoriasis can be challenging to diagnose and treat, and there is limited data to guide this treatment. A flare of the rash may be the initial presentation in some patients who have not had a prior diagnosis. There are many different causes and potential risk factors for a flare of erythrodermic psoriasis. The most common being a prior history of psoriasis, certain medications, and infections. A study of 50 patients with erythrodermic psoriasis found that common precipitating factors were the following: systemic corticosteroids and excessive use of topical steroids, phototherapy complications, severe emotional stress, and preceding illness.
The patient in this study had several precipitating factors worth noting, including recent diagnosis of colorectal cancer and infection with evidence of leukocytosis. She was also under a fair amount of emotional stress given her health issues and prolonged hospital stay. The patient was also receiving several medications that may have increased her risk of a flare, most notably being Vancomycin. Initial treatment is the use of topical corticosteroids and systemic therapy is considered if this does not improve symptoms. Prior case reports have shown that difficult to manage cases can be treated with Acitretin or systemic therapies such as Methotrexate.

An Unusual Presentation of Erythrodermic Psoriasis

Gout is an inflammatory disease characterized by hyperuricemia and monosodium urate crystal deposits, typically affecting peripheral joints at the extremities. We present an atypical case of the disease developing in the fingertip of a 56-year-old Middle Eastern female with a complex history of breast cancer, congestive heart failure, dilated cardiomyopathy, and left arm and hand lymphedema. After months of painful swelling and limited flexion in the left distal index finger, the lesion was initially diagnosed by her primary care provider as an abscess. The persistence of symptoms despite antibiotic treatment prompted further investigation. The patient received an excisional biopsy with histopathological examination, which revealed needle-like amphophilic crystals in the dermis accompanied by foreign body-type giant cells and histiocytes. These results, alongside elevated uric acid levels, confirmed the atypical presentation of tophaceous gout in the left index fingertip. The introduction of 300 mg daily of allopurinol significantly improved symptoms, decreasing joint pain, and the left fingertip lesion resolving. This unusual presentation of gout is secondary to a comprehensive breast cancer medication regimen and lymphedema of the left arm and hand, potentially resulting in the deposition of uric acid in this uncommon location. This unusual presentation of gout underscores the importance of considering gout in differential diagnoses, even in atypical locations.

Atypical Presentation of Gout in the Fingertip: A Case Report

Myelodysplastic syndrome (MDS) is a hematological disease manifesting as ineffective or nonfunctional hematopoiesis. It is characterized by a triad of cytopenia, morphologic dysplasia, and genetic evidence of clonality. Cutaneous manifestations have been associated with MDS in large numbers. We present a case of a MDS diagnosed through initial presentation as a lichenoid dermatitis.

Lichenoid Dermatitis Heralding Myelodysplastic Syndrome

Calciphylaxis is a disorder causing ischemic skin necrosis, typically associated with end-stage renal disease (ESRD) or those receiving dialysis. Occurrence is rare in those without ESRD, and treatment options are limited. This case report describes a patient with calciphylaxis without ESRD or history of dialysis. Treatment with sodium thiosulfate, a first line option, had to be stopped due to metabolic derangements, limiting the healing process. Diagnosis and treatment of this rare disorder is important to prevent further complications that may result.

Non-Chronic Kidney Disease-Induced Calciphylaxis: A Rare Case Report

Title: Pembrolizumab-Induced Epidermotropic CD8+ Dermatitis in a Patient with Multiple Squamous Cell Carcinomas

Background:
Pembrolizumab, a programmed death-1 (PD-1) inhibitor, has been increasingly associated with dermatologic immune-related adverse events (irAEs), varying from benign rashes to severe conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. While the literature describes various dermatologic manifestations like lichenoid dermatitis and granuloma annulare as pembrolizumab side effects, we report a distinctive case of pembrolizumab-induced epidermotropic CD8+ dermatitis in a patient with a history of multiple squamous cell carcinomas (SCCs) and a keratin-positive malignant spindle cell neoplasm. This case adds to the evolving spectrum of pembrolizumab's dermatologic irAEs, underscoring the need for vigilance in patients receiving immune checkpoint inhibitors (ICIs).

A 69-year-old female with a history of multiple SCCs treated across various anatomical sites presented with complaints of a widespread rash. The patient reports that the rash had persisted for 20-30 years but had notably worsened following the initiation of pembrolizumab treatment two years prior. Pembrolizumab was administered as part of her treatment regimen for a keratin-positive malignant spindle cell neoplasm of the right proximal femur. She described the rash as intensely pruritic, worsening during winter months, with mild improvement during summer.

Methods:
Compiled through a retrospective review of medical records with patient consent. Diagnostic assessments were conducted using standard histological and immunohistochemical techniques, supplemented by PCR for T-cell receptor gene rearrangements to evaluate T-cell clonality.

Results
On skin examination, extensive coalescing, ill-defined erythematous patches with associated xerosis were observed. A biopsy of an eczematous lesion on the left lower back was performed to further investigate the rash's etiology. Histopathological analysis revealed hyperkeratosis, parakeratosis, and infiltration of epidermotropic lymphocytes within the epidermis. The infiltrate was predominantly composed of CD8+ T cells. Further molecular studies were negative for clonal T-cell receptor rearrangements.

Conclusion
Given the lack of T-cell clonality and the CD8+ cell-rich infiltrate, a diagnosis of pembrolizumab-induced epidermotropic CD8+ dermatitis was favored over other dermatologic conditions such as mycosis fungoides. The chronicity and the pre-existing nature of the rash, coupled with the exacerbation post-pembrolizumab therapy, underscore its drug-induced origin, distinct from typical dermatologic irAEs reported with ICIs. This case is particularly unique due to the uncommon histopathological feature of epidermotropism of CD8+ T cells, divergent from the more common CD4+ presentations seen in other cases of pembrolizumab-induced dermatitis.

The patient continued with pembrolizumab therapy for her underlying malignancy and her rash was managed with triamcinolone 0.1% topical ointment.This case adds to the literature on pembrolizumab-induced skin reactions, emphasizing the nuanced understanding needed for diagnosis and treatment, particularly in the context of a pre-existing dermatologic condition exacerbated by ICI therapy.

Pembrolizumab-Induced Epidermotropic CD8+ Dermatitis in a Patient with Multiple Squamous Cell Carcinomas

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory disorder of the hair follicle that presents in apocrine gland-bearing areas of the body. It is characterized by nodules, abscesses, fistulae, scars, and sinus tracts in the perineal and perianal regions. The most commonly affected region is the axilla but can also present in the perineal/perianal site in 30-50% of cases. HS cannot be cured, but clinical management can control the disease. HS prevalence is unclear, estimates range from 0.00033% to 4.10% in the US population. Squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer, and accounts for 20% of skin cancer causes. SCC has been documented to be a rare complication of HS lesions. Early detection of SCC in HS patients is important for timely clinical management and treatment. The University of Southern California (USC) Institutional Review Board approved this study. Using de-identified electronic medical records on TriNetX from USC, we used ICM-10- CM codes to identify HS patients who developed skin cancer (basal cell carcinoma, squamous cell carcinoma, melanoma in situ, and malignant melanoma) from 1 day to present day post-HS diagnosis. Kaplan Meier analysis was conducted to compare survival probabilities of HS patients who developed the different skin cancers. Preliminary results show that out of 990 HS patients at USC, 20 patients develop some form of skin cancer in the HS regions (2.02%). SCC was the most common form of skin cancer arising in HS regions. The survival probability was lowest among HS patients who developed SCC (97.08%), compared to BCC (99.35%), melanoma in situ (99.41%), and malignant melanoma (99.60%). Clinicians should be aware of SCC as a complication of HS and be diligent in screening for SCC in management. SCC in HS patients is a rare, but serious complication and delays in diagnosis may lead to worse outcomes.

Next from AMA Research Challenge 2024

Ruptured Intracranial Infectious Aneurysm (IAAs) Mimicking an Expansive Brain Tumor: Endocarditis Case

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