United States

Background
Vasculitis, first described in 1866, describes a group of rare conditions that damage blood vessels leading to multiple organ dysfunction, affecting about 0.01% of the world’s population. Once experienced in practice, is a disease not forgotten. I will present a complicated case of C-ANCA/PR3 vasculitis.
Case Presentation
A 57-year-old female with a 40-pack year history of tobacco use, presented with complaint of fevers, malaise, and a painful purpuric rash, occurring after an earache one week prior. The rash started on her feet, later involving her torso and scalp. Four days after the rash started, she developed odynophagia with oropharynx ulcers.

Labs were consistent with acute kidney injury, anemia, elevated CRP, and sedimentation rate. She had proteinuria, hematuria and her infectious workup was negative. Initial skin biopsy showed a non-diagnostic vascular fluorescence pattern. By hospital day four, the C-ANCA/PR3 labs were positive. Initial chest CT showed diffuse tiny nodular infiltrate with larger irregular ground glass and nodular opacities and no pulmonary embolism. On day four, chest x-ray showed worsening severe diffuse bilateral alveolar lung disease, concerning for diffuse alveolar hemorrhage. 

She developed worsening dyspnea and escalating oxygen needs, requiring transfer to the critical care unit for respiratory failure. With positive C-ANCA/PR3 and her clinical presentation, she received pulse dose steroids with solumedrol 1,000mg for five days. She later had a cyclophosphamide infusion after developing an allergic reaction to rituximab. She required surgical debridement of her wounds and inpatient rehab, eventually being discharged home one month later with reduced but functioning kidneys. Although she was on DVT prophylaxis during hospitalization, she was readmitted two days afterwards with high-risk saddle pulmonary embolism requiring embolectomy.
Discussion
Our patient received pulse dose steroids four days after admission. With high clinical suspicion, it is appropriate to treat without biopsy results. Treatment with steroids, rituximab, and/or cyclophosphamide are common. She required surgical debridement of wounds, inpatient rehab and later an embolectomy. ANCA-associated vasculitis has a two-threefold increased risk of developing a thrombotic event. 

The gold standard for diagnosing vasculitis is kidney, lung, and/or skin biopsies. Due to her clinical picture and bleeding risk, we did not biopsy her kidneys or lungs. Her initial skin biopsy was non-specific, which is an inherent problem with skin sampling. Recognizing the history and physical exam of vasculitis is important for any specialty, allowing prompt laboratory testing, tissue biopsy, and coordination of the multiple specialties involved in the management of vasculitis.

AMA Research Challenge 2024 

When Earache’s Turn to Diffuse Alveolar Hemorrhage

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Infantile Hyaline Fibromatosis Syndrome (also known as IHFS or Inherited Systemic Hyalinosis or ANTXR2-Related Hyaline Fibromatosis Syndrome) is a genetic condition characterized by deposition of hyaline in the skin, muscle, and viscera. IHFS is inherited in an autosomal recessive manner and characterized by mutations in the ANTXR2 (Anthrax Toxin Receptor 2) gene, resulting in the abnormal deposition of hyaline material in skin and organs. Symptoms can subsequently develop in multiple organ systems including rheumatological (progressive joint contractures), musculoskeletal (severe motor disability), immunological (increased susceptibility to infections), dermatological (thick, rough skin, hyperpigmented macules, nodules, and papules), and gastrointestinal (failure to thrive, nausea, vomiting, protein-losing enteropathy, failure to thrive). Complications from these can result in lifelong debilitation and early death.
Per FDA definition, it meets criterion for an ultra-rare condition, affecting fewer than 1 in 1,000,000 births throughout the United States and with fewer than 100 total cases reported worldwide. 

Here we present the case of a 4-month-old with a complicated medical history including painful extremity contractures, global developmental delay, neck hemangioma, and feeding intolerance who initially presented to our institution for abdominal distension. The multi-systemic, progressively worsening nature of her symptoms prompted consultation to inpatient pediatric genetics. Per their recommendation, rapid whole-genome sequencing (rWGS) was performed through Rady Children’s Hospital Institute for Genomic Medicine® in San Diego with the help of the Fabric GEM artificial intelligence (AI) tool. This revealed a homozygous pathogenic variant c.652T>C; P.Cys218Arg in the ANTXR2 gene consistent with IHFS.

This case was significant not only for its extreme rarity, but also its early manifestation of symptoms, wide range of affected body systems, and severity of symptoms, which together present a fascinating diagnostic dilemma for future clinicians that should be taken into consideration. It also highlights the increasing utility of AI-assisted rapid whole-exome sequencing as a diagnostic tool for medically complex patients with hitherto unknown multisystemic hereditary conditions.


An Ultra-Rare Disease: Infantile Hyaline Fibromatosis Identified Using AI-assisted Whole Genome Sequencing

Background

Diabetic kidney disease (DKD) is a complication of diabetes mellitus ultimately characterized by decreasing GFR and gradually increasing levels of proteinuria. In patients with T2DM and proteinuria studies have shown 53% of patients receive a pathologic diagnosis of non-diabetic renal disease when a biopsy is obtained. For this reason, it is important to consider kidney biopsy in diabetic patients with kidney injury and proteinuria whose presentation differs from typical DKD.

Case Presentation

A 77-year-old man with a past medical history including insulin-dependent type 2 diabetes mellitus, hypertension, and stage IV CKD presented with worsening left lower extremity weakness and pain. A history of diabetic retinopathy was notably absent. Additional testing showed an AKI with creatinine of 2.76 mg/dl (baseline of 2.11 mg/dl), hypoalbuminemia of 2.1 g/dl, protein of greater than 1000 mg/dl on urinalysis, and blood pressure of 192/104. A protein/creatinine ratio was elevated at 14.5, from 0.3 one year prior. A 24-hour urine protein was 11g, demonstrating nephrotic range proteinuria. A serologic workup for glomerulonephritis resulted normal C3 and C4, normal kappa/lambda ratio, negative ANA, ANCA, HBsAg, HBc IgM, HCV Ab, HIV, MPO and PR3 ANCA, PLA2R antibody and serum immunofixation demonstrating only hypoalbuminemia and hypogammaglobulinemia. HbA1c over the previous two years had been well controlled, between 5.3 and 6.8%. The patient’s creatinine remained stable at 2.8 mg/dl over the next week, and he was discharged on oral furosemide with plans for kidney biopsy. The presenting lower extremity symptoms were attributed to mild L5-S1 spinal stenosis and left tibial artery disease found on workup. Two weeks later the patient was readmitted with new onset shortness of breath, a 14kg weight gain and a creatinine of 3.99 mg/dl. Physical examination now showed 3+ bilateral lower extremity pitting edema and bibasilar crackles on lung auscultation. Aggressive diuresis was begun. Subsequent kidney biopsy showed C3 glomerulonephritis. The patient was discharged on an appropriate diuretic regimen with plans for outpatient management by nephrology.

Discussion

We present a case of rapidly progressive nephrotic range proteinuria in the setting of longstanding DKD which was secondary to biopsy proven C3 glomerulonephritis. This case underscores the importance of renal biopsy in patients with T2DM who develop renal disease in a pattern atypical of DKD, such as rapid onset nephrotic syndrome or severe kidney disease in the absence of diabetic retinopathy.


C3 Glomerulonephritis in a patient with nephrotic range proteinuria
and longstanding type 2 diabetes mellitus (T2DM)

Monoclonal gammopathy of renal significance encompasses renal disease in the nonlight chain disease manner in the presence of circulating monoclonal antibodies, likely without ongoing bone marrow proliferation. It has an acute course, variable presentation and needs to followed up on.

Monoclonal gammopathy of renal significance

Background

Amoxicillin-clavulanate can cause both liver injury and acute kidney injury. The
majority of the existing literature has described liver-related injury, with fewer
reports noting kidney injury. In this report, we describe a rare case of
concomitant drug-induced liver injury and acute interstitial nephritis as a result
of amoxicillin-clavulanate exposure.

Case Presentation

A 62-year-old male presented to the emergency department with weight loss,
nausea, and diarrhea. Two weeks prior to presentation, he was treated for
sinusitis with a ten-day course of amoxicillin-clavulanate (875 mg-125 mg)
twice daily. The patient was jaundiced, and his abdominal examination
revealed mild distension. Labs included a blood urea nitrogen of 98, creatinine
of 6.6 mg/dL, total bilirubin of 20.5, alkaline phosphatase of 397, aspartate
transaminase of 138, alanine transaminase of 88, and International Normalized
Ratio of 11.4 with pro-time of 127.9. A complete blood count was notable for
9.5% eosinophils, with a total level of 700 eosinophils. A computerized
tomography scan of the abdomen was performed, which revealed gallbladder
wall thickening; subsequent right upper quadrant ultrasonography showed a
minimally distended gallbladder and focally dilated intrahepatic ducts in the
left lobe of the liver. Given concern for renal failure, the patient was admitted
to the ICU. He was started on high-dose methylprednisolone for empiric
treatment of suspected autoimmune hepatitis. Given that drug-induced liver
injury was on the differential, tissue biopsies were obtained. A percutaneous
core kidney biopsy revealed acute tubular injury with bile cast nephropathy,
focal acute tubulointerstitial nephritis, moderate arteriolar hyalinosis, and mild
arteriosclerosis. The liver biopsy showed bile pigment within hepatocytes and
bile canaliculi in peri-central vein areas. These biopsy findings were suggestive
of amoxicillin-induced renal and hepatic injury. The patient was continued on
high-dose IV steroids (which he received for a total of five days) that were
transitioned to an eighteen-day oral prednisone taper. His creatinine gradually
normalized, and the patient’s LFTs remained mildly elevated on the day of
discharge.

Discussion 

This case study demonstrates a rare occurrence in which a patient developed drug-induced liver injury and renal failure. Though antibiotics are widely used to treat infection, their use is not without consequences. In our case, the pathology revealed findings consistent with the immuno-allergic response in amoxicillin-clavulanate drug-induced injury. As this relays the etiology behind the multiorgan failure, tissue biopsy is an essential component in guiding the treatment of patients afflicted with concomitant hepatic failure and renal failure caused by amoxicillin-clavulanate.

Utility of Tissue Biopsy in Amoxicillin-Clavulanate Induced Hepatic Failure and Renal Failure

Single-energy computed tomography (SECT) head is a common diagnostic tool to evaluate for intracranial hemorrhage in emergency settings due to its widespread accessibility and non-invasive nature. However, SECT has densitometric evaluation limitations. For example, hyperdensities on SECT such as blood product and iodine contrast appear similarly. Dual-energy CT (DECT) is a relatively under-utilized imaging modality that has the capability to differentiate between multiple materials. This imaging technique can be extremely useful in identifying materials that are otherwise indistinguishable from standard SECT.

The authors present a case of a patient with findings suspicious of intraventricular and subarachnoid hemorrhage on conventional SECT. The suspected hemorrhage was subsequently ruled out utilizing DECT, as iodinated contrast can be subtracted out, yielding an image that can differentiate iodine contrast from blood or other hyperdense material. The authors discuss the underlying physics, potential advantages, and limitations of the DECT.


Utility of Dual Energy CT Head to Differentiate Myelography Contrast from Intraventricular and Subarachnoid Hemorrhage

Background
Guillain-Barré Syndrome (GBS) is a rare autoimmune disorder of the peripheral nervous system, classically characterized by symmetric, ascending muscle weakness that can progress to life-threatening respiratory depression. Diminished sensation, paresthesia, and autonomic dysfunction may also occur. GBS is a dysregulated immune response triggered by infections.  

Case Presentation
A 15-year-old male with history of depression and substance use presented to the emergency room with one week of bilateral leg weakness, dyspnea, and migratory joint pains. One month prior, he had an upper respiratory infection which resolved spontaneously. Patient was travelling when he developed gait instability, dysarthria, photophobia, and shortness of breath. CT Head was normal. His respiratory function worsened, requiring escalating oxygen requirements, followed by acute deterioration of mental status. He was sedated, put on ventilatory support, and transferred to our critical care unit.  

Neurological exam revealed hypotonia, present reflexes, and poor muscle coordination out of proportion to muscle weakness, which initially suggested functional etiology. MRI and MRA brain and spine were unremarkable. Cerebral spinal fluid studies revealed albuminocytologic dissociation and elevated inflammatory markers (IL-6, IL-8). Potential autoimmune, paraneoplastic, rheumatologic, demyelinating, infectious, and toxic causes were ruled out. After unsuccessful extubation attempts, serial examination revealed involvement of cranial nerves VII, IX, and X. 

He received a three-day course of intravenous immunoglobulin (2g daily) and gabapentin. Major complications included hospital acquired pneumonia and decompensated psychiatric state (worsening mood, panic attacks). Over three weeks, his mental status normalized, and he regained significant muscle strength and coordination. After confirming regained diaphragmatic function on ultrasound, he was extubated and weaned to room air. The patient was then transferred in stable condition to an acute rehabilitation center. 

Discussion
In pediatric patients, clinicians should conceptualize GBS as a spectrum of neurological symptoms that can differ from the typical ascending pattern but remain responsive to immunoglobulin treatment. This case proved unique because our patient’s history aligned with classic GBS, but he did not have expected radiological findings and patchy, rather than length-dependent, motor and sensory symptoms. His presentation had mixed features of multiple GBS subtypes, including Acute Motor Axonal Neuropathy and Multifocal Acquired Demyelinating Sensory and Motor Neuropathy. In addition to diaphragmatic weakness, patients can develop cranial neuropathies that prolong need for mechanical ventilation and increase risk of pneumonia. Lastly, in adolescents with prior psychiatric history, GBS can acutely exacerbate mood and anxiety symptoms which may be falsely attributed to functional neurological disorder.

An Eccentric Case of Guillain-Barré Syndrome in an Adolescent Male

An acute dilated pupil signals dysfunction of the third cranial nerve or sympathetic/parasympathetic pupillary pathways. Life-threatening etiologies of third nerve cranial impairment include uncal herniation, cerebral aneurysm, or another space-occupying lesion. Consequently, the finding of an acute, unilateral, dilated pupil warrants immediate clinical evaluation and neuroimaging.
However, anisocoria without findings of oculomotor deficits is rare in compression-induced third cranial nerve palsies but is rather commonly associated with pharmacological etiologies or Adie’s pupil. Specifically, anticholinergics allow unopposed sympathetic stimulation of the dilator pupillae muscle, resulting in a dilated pupil. Administration of ipratropium through a face mask inhaler is common in intensive care respiratory management. However, masks are susceptible to leakage and displacement. Pupillary dilatation secondary to ipratropium has been described but is not widely known. We presented a case report where an unilateral anisocoria is secondary to contamination of ipratropium to the right eye.

Ipratropium-Induced Anisocoria due to an Ill-Fitting Face Mask Inhaler

Abstract: 

Background: 

Myelitis is a debilitating neurological condition characterized by inflammation and demyelination of the spinal cord. It leaves two-thirds of patients with moderate to severe residual disability. Generally occurring independently, often as a complication of infection, it can also be a component of neuro-inflammatory spectrum disorders like multiple sclerosis, neuromyelitis Optica spectrum disorder (NMOSD), acute disseminated encephalomyelitis, and MOG antibody disease. NMOSD is distinct by the presence of aquaporin-4 IgG antibodies (AQP4-IgG) and has an estimated global prevalence of 1 in a million, predominantly affecting females. 

Case presentation: 

A 59-year-old female with a questionable history of Brown-Séquard syndrome in 2004, for which she avoided surgery due to concerns about losing mobility, presented with acute neck pain following a bug bite on the back of her neck, with pain and tingling sensation in both the hands. An MRI of the neck revealed T2-weighted hyperintense signals from the cervico medullary junction to the upper border of T1, indicating spinal cord edema(Figure 1). Blood work for paraneoplastic syndrome(s) was negative but the presence of AQP-4 antibodies confirmed the diagnosis of NMOSD. She was treated with a 5-day course of high-dose intravenous methylprednisolone and plasma-exchange, leading to significant symptom improvement. She was placed on rituximab monotherapy (1000 mg once every 6 months) for chronic treatment. 
case.png

Discussion: 

NMOSD is definitively diagnosed based on AQP-4 antibodies in serum and CSF with signs of area postrema syndrome and acute myelitis (2015 diagnostic criteria). Moreover, this patient's symptoms improved following immunotherapy, but not anti-infective medication. Intravenous methylprednisolone is typically used to treat acute NMOSD episodes. If unresponsive, plasma exchange can be added. Acute attack outcomes have improved in single case series by experimental therapies like IVIG, anti-CD20, and anti-complement therapy. 

Relapses have reduced with immunosuppressive maintenance therapy using rituximab, azathioprine, mycophenolate mofetil, and oral prednisone. Shi Z et al., with 281 Chinese NMOSD patients, showed azathioprine and mycophenolate mofetil lowered disability and relapse rates. Yaguchi H et al. found cyclophosphamide (monotherapy or in combination with methylprednisolone) effective in both acute and chronic phases. Approved immunotherapies, inebilizumab, eculizumab, and Satralizumab, reduce the relapses and the cumulative impairment. Newer biologics (theravulizumab, ublituximab, aquaporumab, and sedelestat) are undergoing review for use in NMOSD. 

Conclusion: 
For atypical presentation of NMOSD, a high index of suspicion is needed for early treatment and better patient outcomes. Although novel treatment modalities provide a hope for more effective treatment, more trials are required to estimate their safety and efficacy.

Neuromyelitis Optica Spectrum Disorder: A case report and a review of treatment modalities

Background 
Immediate reperfusion is vital to treating an acute ischemic stroke (AIS). Tenecteplase can be used for thrombolysis. However, there is a chance of early recurrence of ischemia which can affect the high cervical spinal cord (HCSC) which often gives a bad prognosis but with appropriate management, a good clinical outcome can still be expected. 

Case Presentation 
A 69-year-old female with no known comorbidities suffered an HCSC infarct after treatment with tenecteplase for an acute ischemic stroke. 

She presented with sudden pain in the right neck with nausea, diaphoresis, and dizziness. Neurologic examination was significant only for a left facial droop. CT angiogram showed an occlusion of the right vertebral artery at V3-V4 segment. She was given IV Tenecteplase within 4.5 hours of onset. 

Few hours later, she developed difficulty breathing. She had bilateral diaphragmatic paralysis resulting in respiratory acidosis requiring mechanical ventilation. Additionally, she developed quadriplegia. MRI brain showed an HCSC infarction. She was on ventilatory support for 2 months due to diaphragmatic compromise. She underwent a tracheostomy and percutaneous endoscopic gastrostomy. Multiple bronchoscopies were done to manage mucous plugs and retained secretions, and she received antibiotics for ventilator-associated pneumonia. 

Despite all complications, she was weaned to a speaking valve and eventually was able to communicate. Modified barium swallow showed tolerance to oral intake. Tracheostomy was successfully decannulated thereafter. 

She was eventually discharged with a motor exam of 2-3/5 in all extremities with no other focal neurologic deficits. 

Discussion 
The patient suffered from a mild ischemic stroke. Alteplase is the only approved thrombolytic drug by the Food and Drug Administration (FDA) for the treatment of AIS. If given within 3-4.5 hours of onset, it can prevent further disability. 

Coming in during the therapeutic window for thrombolysis, she was given tenecteplase, a modified variant of alteplase. Tenecteplase is FDA-approved for thrombolysis in acute myocardial infarction but has found off-label use for AIS. 

Early recurrence of ischemic stroke has been reported after alteplase. For tenecteplase, there are instances of expansion of the original infarct after thrombolysis but no documented report of an HCSC infarct as of this writing. Nevertheless, due to the similar pharmacokinetic properties of tenecteplase to alteplase, such a phenomenon of ischemic stroke recurrence may occur. 

Acute spinal cord infarct is a rare occurrence and usually involves non-cervical territory. It may be associated with episodes of hypotension and may present with quadriplegia and diaphragmatic paralysis which were all found in this patient. 


Risks of Thrombolytic Therapy: Uncommon Complications with A Good Outcome

Miller Fisher Syndrome (MFS) is an uncommon neurological disorder with an estimated yearly incidence of 1 in 1,000,000 in the United States. MFS is a variant of Guillain-Barre syndrome (GBS) characterized by ophthalmoplegia, ataxia, and areflexia, likely preceded by either a recent infection of the upper respiratory or gastrointestinal tracts, or vaccination. This syndrome most commonly affects adult males with a median age of 44 years. Here we want to draw attention to a rare case of MFS with atypical presentation in a 60-year-old female patient who presented to the Emergency Department (ED) with a medical history of hypertension and diabetes mellitus with complaints of blurred vision and walking difficulty for 2 days. She developed respiratory weakness requiring Intensive Care Unit (ICU) admission, and hyporeflexia, bilateral ptosis, and ophthalmoplegia subsequently. Provisional diagnosis of MFS was made upon cerebrospinal fluid (CSF) analysis which was later confirmed by the presence of Anti-GQ1b antibody. A single dose of Intravenous Immunoglobulin (IVIG) was sufficient to stabilize the patient’s condition, allowing her to be moved out of the ICU. Given the favorable prognosis of this disorder, early identification and effective drug treatment would minimize unnecessary medical interventions, curtail expenditures, and ease psychological distress.

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