United States

Resistant hypertension is defined as uncontrolled blood pressure (BP) despite treatment with three or more medications at optimal doses. Hypertensive urgency is characterized by a severe elevation in BP without evidence of end organ damage. Ultimately, this can lead to hypertensive emergency manifesting as neurologic deficit, hypertensive retinopathy, intracranial hypertension, aortic dissection, myocardial ischemia, or hypertensive nephrosclerosis. 
A 55-year-old female with a medical history of longstanding hypertension, hypertensive cerebrovascular accident, CKD IV, hyperparathyroidism status post parathyroidectomy, and left ICA aneurysm presented to the emergency department after an office visit where her systolic BP was 260. She experienced intermittent headache, diaphoresis, and blurry vision for several months prior to presentation. Despite adherence to diet, exercise, and a regimen of losartan 50mg, carvedilol 25mg, isosorbide dinitrate/hydralazine 20-37.5mg, and nifedipine 90mg, her BP remained uncontrolled for years. Family history included accelerated hypertension, kidney disease, and stroke before age 50.
On exam, the patient was comfortable, but diaphoretic with BP 267/140, heart rate 68, respirations 16, and oxygen saturation of 99% on room air. Cardiac exam revealed S3 and S4. Extraocular movements were intact and fundoscopic exam was limited. Laboratory values revealed a creatinine 1.8mg/dL, 2+ urine protein, parathyroid hormone of 367.2 pg/mL and a calcium of 9.1mg/dL. Other values were within normal limits. Nicardipine infusion improved BP to 182/114, and she was restarted on her home regimen with continued improvement over the next several days.
Further work up for secondary hypertension revealed normal TSH and aldosterone. Abdominal imaging showed normal adrenal glands and moderate-to-severe left renal artery stenosis. Serum metanephrines were 1.2 times the upper limit of normal, and urine metanephrines were 1.4 times the upper limit of normal. 
Renal angiogram revealed proximal left renal artery stenosis and was less suggestive of fibromuscular dysplasia. A stent was placed in the left renal artery, resulting in a reduction of systolic pressure from 150-200 during hospitalization to below 130 at outpatient follow-up. 
A hypertension workup for etiologies was essential for this patient, and ultimately revealed several possibilities including MEN IIA, fibromuscular dysplasia, and renovascular hypertension. This underscores the importance of comprehensive assessment of resistant hypertension and hypertensive urgency to mitigate complications. In this patient with chronic, multi-organ injury due to hypertension, we were able to identify a reversible cause with potential benefits to morbidity. Identifying causes of hypertension can help avoid unnecessary pharmacotherapy and long-term sequelae associated with severely elevated blood pressure.

AMA Research Challenge 2023

When to dig deeper: Unraveling Secondary Hypertension in the Context of Hypertensive Urgency

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Kikuchi-Fujimoto disease is a form of benign necrotizing lymphadenitis also known as histiocytic necrotizing lymphadenitis. While Kikuchi disease is a globally prevalent disease, it is predominantly seen in the Asian population. Etiology can be traced back to dysregulated immune responses triggered by viral or autoimmune factors. Here we present a case report to emphasize the importance of considering Kikuchi disease and possible etiologies, highlighting the need for increased awareness and recognition of this rare condition. A 28-year-old female with a history of hypothyroidism, IBS, and GERD complained of sore throat, intermittent epigastric pain, mild heartburn, and fever and was taking PPIs without any improvement. Abdominal USG was negative for any pathology. She presented with bilateral enlarged cervical lymph nodes and worsening of symptoms 1.5 months later. Ciprofloxacin was prescribed which failed to improve the symptoms. CT scan of the neck showed an enlarged thyroid gland with diffuse lymphadenopathy. Labs showed elevated TSH, for which the levothyroxine dose was increased, despite that she still continued to have symptoms. LDH and CRP were normal. Rheumatology, oncology, and infectious disease specialists were called upon for further evaluation. Excisional Lymph node biopsy showed areas of extensive necrosis with karyorrhectic debris, surrounded by histiocytes and small lymphocytes, suggestive of necrotizing lymphadenitis, specifically consistent with Kikuchi disease. Immunophenotyping by flow cytometry demonstrated normal CD4+ and CD8+ T cell populations without any evidence of clonal lymphoid expansion. AFB and GMS stains were negative for infection. Hydroxychloroquine 200 mg twice daily was given, which resulted in the resolution of her symptoms. Kikuchi disease’s origins can be traced back to Japan, where it was initially documented. More prevalent in the young female Asian population under the age of 30. It presents as tender, enlarged nodes, primarily in the cervical region along with lymphadenopathy, fever, erythematous rash, joint pain, fatigue, arthritis, and hepatosplenomegaly. It becomes important to consider Kikuchi disease in patients presenting with symptoms that can be attributed to sore throat related to GERD, followed by the development of fever with cervical lymph node enlargement.

Unusual presentation of sore throat with bilateral lymphadenopathy in a hypothyroid patient: Kikuchi Fujimoto Disease, A case report.

Background: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary early-onset vascular disease causing recurrent ischemic subcortical infarcts. Common presentations include transient ischemic attacks (TIA) and strokes (74.36%), cognitive impairment (69.23%), psychiatric disturbance (25.64%),(25.64%) and migraines (15.38%). In the realm of medical mysteries, CADASIL stands as a perplexing and devastating hereditary disease. This case aims to highlight the unique presentation of CADASIL with facial palsy and the need for a multidisciplinary approach to management. 
Case: A 52-year-old male with a family history of strokes at a young age in his father and paternal grandfather, presented to a neurology clinic for left facial droop and drooling. Brain MRI showed extensive periventricular and subcortical white matter disease, including the external capsule and subcortical white matter of the temporal lobe. Findings were suggestive of small vessel vasculopathy. A cerebral angiogram showed that all large extra and intracranial vessels were patent without evidence of aneurysm formation. There was no obvious evidence of beading of the distal intracranial vessels. CSF studies were normal. The NOTCHNOTCH 3 mutation was sent to test for CADASIL, which came back positive. The patient was started on aspirin (aspirin 81 mg) and atorvastatin (20 mg) daily. The patient was counselled on the possibility of getting an ischemic or hemorrhagic stroke. Aspirin and atorvastatin were continued, a neuropsychological evaluation was ordered and CADASIL genetic counselling and testing was offered to him and his children. Over several years, the patient developed several strokes and seizures due to infarcts. He also developed Intraparenchymal haemorrhage complicated by dysphagia requiring a feeding tube. Due to his severe physical debility, he was discharged to a nursing home for rehabilitation, where he did not improve with therapy and remained bedbound. He was discharged home with his family.
Conclusion: CADASIL can present as a diagnostic challenge due to its common presentation with migraines, TIA, and strokes with or without risk factors. This unique presentation of CADASIL with facial palsy highlights the importance of emerging atypical presentations and the need for a detailed history of neuroimaging, family history, and personal history of neurovascular events. By accurately diagnosing the condition, patients and families can be counselled on the disease course and genetics. Management requires a multidisciplinary approach with neurology, genetic counselling, physical therapy, psychology, and psychiatry to improve the patient’s quality of life.


CADASIL Presenting With Facial Palsy –A Case Report and Comprehensive Review


Introduction: Posterior reversible encephalopathy syndrome (PRES) is a distinct clinical syndrome with characteristic radiographic abnormalities on imaging. Although the pathogenesis of PRES is not fully understood, abnormal cerebral blood flow regulation likely contributes to its development. As arterial blood pressure rises in the cranium, the blood-brain barrier is disrupted. Efflux of fluid into the brain parenchyma, producing vasogenic edema. Many factors can lead to the development of PRES including and not limited to: hypertension, acute kidney injury, sepsis, illicit drug use, and pharmacological agents. Toxins and substances that increase the sympathetic activity of the CNS system can drastically potentiate the effects of PRES. We report a case of PRES secondary to these conditions.

Case: 64-year-old female with PMHx of hypertension, atrial fibrillation, and recurrent UTI who presented to the hospital due to altered mental status. On the morning of admission, the patient was found confused, nonverbal, and tremulous in her left arm by the patient’s daughter. Furthermore, the patient's daughter noticed empty bottles of tramadol and kratom around the patient. On ED presentation, the patient was hypertensive and afebrile. Urinalysis revealed heavy pyuria, and urine culture showed 100,000+ ESBL-positive E.coli. The patient was started on IV antibiotics. CT head was negative for hemorrhages/infarct. On day 2, the patient was found confused, ANOx1, and unable to follow commands. Bedside EEG was inconclusive for seizures. CT Head Stroke w/o contrast significant for no acute intracranial hemorrhage and mild to moderate vasogenic edema involving the bilateral frontal lobes. The patient loaded on Kreppa. On day 3, the patient was observed at the bedside to have multiple seizures. MRI head was remarkable for vasogenic and cortical edema within the bilateral, occipital, and parietal subcortical white matter suggesting PRES. On day 4, the patient was transferred to ICU. She was intubated, sedated, and placed on mechanical ventilation. The patient started on IV seizure medication and prophylaxis. Continuous EEG is remarkable for ninety-three focal seizures, the majority are from proper posterior quadrant onset during the next twenty-four hours. On the subsequent days, the patient was detected to be actively seizing on continuous EEG despite anti-seizure medications, being intubated, sedated, and on mechanical ventilation.


Discussion/Conclusion: Case reports and studies have been reported to link multiple agents causing seizures and PRES. Though not fully understood, toxins that increase the sympathetic activity of the CNS system can drastically potentiate the effects of PRES. Identifying, treating, and managing the underlying etiology, in addition to careful treatment of hypertension and seizure management is crucial for the management of PRES. The prognosis of PRES is typically favorable if recognized and treated early, with symptom improvement or resolution in a few days to several weeks.

A Multifactorial Analysis of Posterior Reversible Encephalopathy Syndrome 

Acute pancreatitis is a common condition with various possible etiologies. The most common causes include gallstones and alcohol, followed by metabolic, structural, and iatrogenic causes accounting for 20 – 25% of the cases. Hyperlipidemia in the form of hypertriglyceridemia and chylomicronemia accounts for 15-20% of the total cases attending lipid clinics in US. The conventional methods of treatment of severe hypertriglyceridemia are dietary restriction and lipid lowering medications, mainly fibric acid derivatives. In the medical literature, use of insulin infusion to treat hypertriglyceridemia induced acute pancreatitis is still under reported.

Hypertriglyceridemia induced acute pancreatitis treated with parenteral insulin; a possible alternative to plasmapheresis in resource limited setting: a case report

Introduction:
Purple Urine Bag Syndrome (PUBS) is a rare manifestation of bacteriuria that results in a pathognomonic purple discoloration of the urine catheter and collection bag. The accepted hypothesis for this phenomenon is bacterial production of pigment molecules in alkalotic urine. It is historically associated with females with prolonged indwelling urinary catheterization and chronic constipation. Here, we describe an atypical case of PUBS. 

Case Presentation:
A 73-year-old female with prior ischemic stroke, atrial flutter, and urinary retention presented to the emergency department with decreased urine output and lower abdominal pain. She had an indwelling foley catheter exchanged one month prior to presentation. She denied fevers, chills, and constipation. Physical exam revealed a confused woman with dry mucous membranes and suprapubic tenderness. Dark brown urine was present in a purple foley bag and tubing. Labs were significant for serum creatinine of 2.72 mg/dL, BUN of 51.4 mg/dL, and leukocytosis of 13.3 TH/cmm. Foley catheter was exchanged. Urinalysis revealed elevated protein, pH of 8.5, bacteria, and leukocytes. Ceftriaxone and vancomycin were started for treatment of sepsis secondary to urinary tract infection (UTI). Urine culture grew Citrobacter freundii and Escherichia coli, so antibiotics were deescalated to ceftriaxone alone. Her suprapubic pain and mental status improved, and her acute kidney injury resolved after intravenous fluids. Upon discharge, she was scheduled for follow up with Urology for further testing for possible neurogenic bladder and recommendations regarding indwelling foley catheter.

Conclusion:
Much about the manifestation of PUBS is still unknown. It is thought that constipation creates an environment where dietary tryptophan is increasingly produced, converted into indole by intestinal bacteria, and then absorbed by the portal circulation to be conjugated into indoxyl sulfate. Bacteria with phosphatase and sulfatase enzymes convert this compound into indoxyl which oxidizes in alkaline urine to pigmented indirubin and indigo. These pigments interact with the plastic in the catheter bags to produce a violet hue. However, this has not been uniformly proven in all cases. Additionally, many studies have shown that constipation is not always present either. The only true requirements are an indwelling catheter and UTI. Because PUBS is typically observed in patients with recurrent UTIs, it is important to consider modifiable risk factors to prevent future infections, such as prompt replacement of indwelling catheters and bowel regimens. Healthcare workers and patients can be assured that although unusual, the purple discoloration of PUBS is generally benign and not indicative of any underlying pathology except bacteriuria or UTI.

A Colorful Case of Purple Urine Bag Syndrome

Background
Streptococcus agalactiae, or group B streptococcus (GBS) is a pathogen that can cause a wide array of clinical syndromes, especially in immunocompromised patients. This rarely being the etiology of meningitis complicated by cerebral abscess and endocarditis concurrently with septic emboli.

Case Presentation
We present the case of a 62 year old female who was brought to the ED due to altered mental status, and was found to be in nonconvulsive status epilepticus. Patient had poor dentition and imaging showed an avidly enhancing mass in the right parietal gland. She was treated for status epilepticus while further infectious workup was performed. Lumbar puncture was suspicious for bacterial meningitis and the patient was treated with empiric antibiotics. CSF cultures grew GBS. MRI brain was performed which showed abnormal air/fluid in the left parietal region which was suspicious for cerebral abscess. Drainage was deferred due to antiplatelet and anticoagulant use. Patient was stabilized and discharged to a rehab facility. The patient later developed AMS and decompensated. She was found to have bacterial endocarditis and TAVR was performed and the patient was treated with outpatient IV antibiotics. Follow-up MRI showed absence of any brain lesions and the patient gradually recovered. 

Conclusion 
Meningitis with GBS is rare but may be seen with increasing frequency in the adult population. Cerebral abscess secondary to strep agalactiae meningitis is a incredibly rare phenomenon. Furthermore, our patient may have developed endocarditis secondary to her poor dentition leading to septic emboli, which lead to her osteomyelitis. Overall, the case highlights the need to be cognizant of abnormal presentations of disease and treat appropriately and strictly adhering to the infectious disease guidelines. 


Streptococcus agalactiae meningitis and endocarditis complicated by septic emboli and a possible cerebral abscess in an elderly patient

Background: Metformin is a widely prescribed medication for the management of type 2 diabetes. It is known to have a high safety index, however it can cause serious adverse effects such as lactic acidosis, particularly in patients with chronic kidney disease. Elderly patients are at higher risk of developing Metformin-Associated Lactic Acidosis (MALA) due to aging kidney. We aim to highlight the importance of early adjustment of metformin and propose development of guidelines with higher estimated glomerular filtration rate (eGFR) for deprescribing metformin in older adults in contrast to younger population. 

Case Presentation: An 82 year old male with a past medical history of Diabetes, Chronic kidney disease 2, Atrial fibrillation on apixaban, Stroke and Chronic stage 4 sacral decubitus ulcer was sent to the emergency department (ED) for altered mental status. He was admitted to the intensive care unit for management of septic shock, PEA cardiac arrest and acute hypoxemic respiratory failure requiring intubation. Labs showed lactic acidosis and anion gap metabolic acidosis in the setting of no infectious source. Patient had chronic kidney disease with acute renal failure on metformin. He was diagnosed with Metformin Associated Lactic Acidosis. 

Discussion: This case highlights the potential risks associated with metformin use in older adults with CKD and AKI from infections, dehydration and decreasing oral intake due to acute illness, aging or dementia. There are expected physiological changes in the aging kidney including cellular dysfunction and nephrosclerosis that can cause unexpected kidney injury in older adults causing their eGFR to drop acutely. Age-related changes in renal function and decreased clearance of drugs place elderly patients at higher risk of developing MALA. New guidelines for higher eGFR for deprescribing metformin should be considered in older adults. This could prevent morbidity, mortality and adverse outcomes in the frail older diabetic population. 


Metformin Associated Lactic Acidosis in an Elderly Patient: A Case Report

Background
In the United States, approximately 294,000 suffer from spinal cord injury (SCI). There are an estimated 17,810 new cases each year. People with SCIs are susceptible to the same medical conditions as their non-injured counterparts. Some conditions may be more difficult to diagnose in SCI patients based on presenting symptoms.

Case Presentation
A 70-year-old female with past medical history of T4 paraplegia presented with subacute onset of pruritic rash and acute onset shoulder and orofacial weakness. The rash began on her shoulders before spreading diffusely; an initial outpatient trial of oral and topical steroids did not improve symptoms. Two weeks following the rash onset, the patient noted proximal shoulder weakness described as 30% of her baseline strength. Notably, the patient’s husband passed away two weeks prior to presentation. Review of systems was positive for diminished appetite, fatigue, chills, abdominal distension, constipation, weakness, and rash. On physical exam, the patient had numerous pink/violaceous papules and plaques noted on extremities, chest, back, and head. Skin biopsy showed dermatomyositis. Steroids were started and rheumatology workup was significant for positive antinuclear antibody and elevated creatinine kinase. CT abdomen/pelvis showed enhancing omental nodularity, concerning for carcinomatosis. Tumor markers were notable for elevated CA-125. Omental biopsy revealed metastatic adenocarcinoma of Mullerian origin. Upon discharge, the patient was diagnosed with paraneoplastic dermatomyositis secondary to ovarian cancer with oncology follow-up and steroid therapy for dermatomyositis.

Discussion
It is important to keep a broad differential diagnosis in patients presenting with a chief complaint of weakness, particularly in those with SCI in which new onset weakness may be difficult to assess clinically. Dermatomyositis and Polymyositis are important diagnoses to consider, particularly when the weakness is symmetric and proximal. Patients with SCI may not note these hallmark symptoms, so one must utilize the full physical exam. Classic dermatomyositis skin findings can clue the examiner into the potential diagnosis even in the absence of assessable weakness. In adult-onset disease, the risk is approximately 20%–32% for an associated internal malignancy, making it imperative to make a diagnosis to ensure a prompt oncologic workup is completed. Additionally, weakness is a commonly noted symptom of bereavement, which may lead providers to attribute similar symptoms to somatic complaints when social history aligns. Our case illustrates the importance of maintaining a broad differential in patients whom weakness is difficult to elicit and not anchoring on social history when evaluating a subjective chief complaint like weakness.


Weakness in a patient with spinal cord injury: A broad differential is key


Background
The recent regulation of xylazine, a veterinary sedative and analgesic, has exposed its escalating threat to public health. The growing misuse of xylazine due to its sedative effects and its concomitant use with opioids like fentanyl for cost-cutting further intensifies the opioid crisis. Xylazine use poses significant risks, including overdose, addiction, withdrawal, and severe tissue damage at the injection site. Xylazine acts on the central nervous system via alpha-2-receptor agonism. This case highlights the challenges of outpatient management of xylazine withdrawal and wound care, emphasizing the immediate need for effective interventions to address this public health issue.

Case Presentation
We report the case of a 41-year-old female on a methadone maintenance program who presented to the clinic with a large necrotic wound on her left forearm. The patient reported injecting xylazine into the wound multiple times daily. Initial assessment revealed a multistage wound with eschar covering a significant portion of the forearm. Despite the alarming features of the wound, the patient declined hospitalization and residential drug treatment. A decision was made to closely monitor her as an outpatient with treatment goals to discontinue xylazine use, prevent wound infection, and facilitate wound healing. The treatment plan included doxycycline for infection prophylaxis and wound care with collagenase, followed by Medihoney dressing. Withdrawal symptoms were managed using clonidine, gabapentin, and ondansetron, which were prescribed cautiously due to their abuse potential. With pharmacologic interventions and close outpatient follow-up, the patient stopped using xylazine and adhered to the treatment plan. The wound transitioned from necrotic to viable tissue, but an exposed extensor tendon necessitated a referral to a higher level of care, which the patient declined.

Discussion
Managing xylazine withdrawal and xylazine-associated wounds in an outpatient setting is challenging due to limited guidelines, medication misuse potential, and patients' hesitance toward hospitalization. Tailored treatment plans, close monitoring, and patient collaboration are vital. Wound care is crucial in preventing further deterioration and facilitating tissue regeneration. However, specialized management for the exposed extensor tendon was declined. Managing xylazine withdrawal with limited medication quantities and close monitoring presented additional challenges. The success of this outpatient management relied on collaboration and communication, fostering compliance and therapeutic alliance. This case highlights the challenges of managing xylazine misuse and emphasizes the need for individualized approaches and further research.

Managing Xylazine Misuse in Outpatient Settings: Challenges and Interventions

Metaplastic breast cancer (MBC) is a rare, aggressive subtype that often presents unilaterally as a high-grade large tumor with solid or cystic components compared to other forms of breast cancer. MBC was only recently recognized as a distinct pathologic diagnosis, so knowledge is limited in its pathogenesis, patient demographics, presentation, or standard treatment guidelines. Although knowledge is limited, MBC is most commonly diagnosed in women between the ages of 55 to 60 and is often chemotherapy resistant and reoccurs. MBC carries a poor prognosis with a survival rate of less than 1 year for patients with distant metastasis. We present a case of MBC diagnosed in a 28 year-old Afghani female that presented with increasingly worsening swelling and erythema of her left breast, without any other classical signs of breast cancer including skin dimpling, nipple changes or discharge, or fever. This patient demonstrates an unusual presentation of rare metaplastic breast cancer in a younger patient than normally diagnosed, further showing the unpredictable nature of this disease. Further research to improve diagnosis, treatment, and survival rates of patients with metaplastic breast cancer is needed with further exploration of targeted therapies and increased familiarity of the disease for the publication of standard treatment guidelines. 


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When to dig deeper: Unraveling Secondary Hypertension in the Context of Hypertensive Urgency

Next from AMA Research Challenge 2023

Unusual presentation of sore throat with bilateral lymphadenopathy in a hypothyroid patient: Kikuchi Fujimoto Disease, A case report.