Faculty Bibliography

Learning Objective #1: Recognize the clinical & laboratory presentation of chronic nitrious oxide abuse. CASE: 51yo F with history of hypothyroidism and anxiety presented to the ED after being brought in from the street by police. Over the course of the past month, she reported mental slowing and relative weakness, numbness and tingling in her hands and feet, incoordina-tion of fine motor movements and gait abnormalities. ROS was otherwise negative. She denied any visual or auditory hallucinations, SI or HI. Past medical, surgical and family history were unremarkable. She lives in Manhattan with her boyfriend, who was apprehended by authorities under similar circumstances. She takes daily synthroid and Valium and reported distant history of alcohol use 1 month ago. VS WNL. She was alert and oriented to self and location but believed the year was 1920 and exhibited word-finding difficulty. Physical exam revealed grossly normal cranial nerve functions without dysarthria, and normal strength, sensation, and bulk muscle tone. She had a negative Romberg exam but exhibited some impairment of proprioception sense in fingers and toes, particularly with downward movement. She was able to stand up and walk unassisted with a wide-based and unsteady gait. BMP, LFTs, coags, TSH, CPK were normal. CBC was remarkable for a leuko-penia to 1.7 (ANC 250), Hgb 12.5 with an MCV of 87.8, platelets 166. Iron studies were suggestive of anemia of chronic disease, with LDH 240 and reticulocyte index was 0.9. Vitamin B12 returned low at 183 ng/L and homocysteine and methylmalonic acid levels were elevated at 191 umol/L and 0.9mmol/L respectively. Utox was positive for benzodiazepines. Many diagnoses were considered including MS, tertiary syphilis, and GBS, but the patient ultimately admitted to abusing up to 8-10 containers of whippets (small pressurized containers containing N2O) daily for the past month. Toxicology and neurology were consulted and her physical exam and lab derangements were thought to be secondary to a functional B12 deficiency, for which she was initiated on IM repletion. An MRI brain and spine was ordered but she ultimately left AMA. She intended on cutting back on whippets use and expressed a desire to "clear her head" on her walk home. IMPACT/DISCUSSION: Nitrous oxide abuse has recently gained popularity as a recreational party drug due to its availability. When inhaled, it causes euphoria, analgesia within seconds. Chronic use leads to toxicity through the oxidation of cobalt ions in vitamin B12, hence causing inactivation. This causes reduced recycling of homocysteine to methio-nine, thereby preventing methylation of myelin proteins. Patients present with fatigue, weakness, poor balance and paresthesias and MRI imaging may show posterior column hyperintensities on T2W imaging. High-dose intramuscular B12 replacement is recommended, but recovery may ultimately be slow and incomplete.
Conclusion(s): N2O is a rare cause of functional B12 deficiency, pernicious anemia and peripheral neuropathy

Learning Objective #1: Discuss typical, atypical clinical & laboratory presentations of acute mononucleosis Learning Objective #2: Review indications for treatment beyond supportive care CASE: A 33 year-old female with 1 prior spontaneous abortion presented with facial swelling, arthralgias and fevers to 102F for 2 weeks. The patient reported environmental exposures as a native of Australia such as outbreaks of Ross River Fever, encounters with flying foxes, a layover in Hong Kong, and a child with a febrile illness. She sought outpatient care and initial bloods revealed WBC 2.52K/uL, platelets 105K/uL and AST/ALT 88/70 ALP 117 U/L. She was prescribed antibiotics without effect. A week later, she developed pleuritic chest pain, was found to have a small pericardial effusion on outpatient echocardiogram and referred to the Emergency Department. Triage vitals were normal. Her exam was notable for periorbital edema, cervical lymphadenopathy and pain in bilateral wrists without effusion. Labs showed recovering blood counts (WBC 9.3K/uL Hgb 13.1g/dL Plt 157 K/uL), unremarkable UA, microalbumin/creatinine ratio and CK, but worsening LFTs with AST 505 ALT 578 ALP 788 U/L. She was admitted for further work-up with rheumatology and infectious disease input. While hospitalized, the patient developed new night sweats and a sore throat. Repeat echocar-diogram revealed a trace pericardial effusion and abdominal ultrasound was normal. C3/C4 levels, beta-2 glycoprotein, cardiolipin, Ro/La, lupus anticoagulant, histone, centromere, and mitochondrial antibodies all returned negative, as did respiratory viral panel, HIV, hepatitis serologies, thick and thin smears, Lyme, Anaplasma and Babesia serologies, Ross River fever, Dengue and Chikungunya. ANA titer and dsDNA Ab were < 1:40 and 9 respectively, but EBV viral capsid IgM returned positive consistent with acute mononucleosis. IMPACT: The triad of acute EBV is well known, but atypical presentations provide diagnostic challenges and warrant further evaluation DISCUSSION: The triad of acute Epstein-Barr viral infection involves high fevers, lymphadenopathy, and pharyngitis, all present in our patient. However, she also exhibited less typical disease features. Her periorbital edema, known as "Hoagland's sign," is caused by viral replication obstructing lymphatic drainage of the nasopharynx. Similarly, infected tonsillar B-cells instigate secretion of polyclonal antibodies (including heterophile and non-specific autoantibodies). This process is normally accompanied by leukocytosis with atypical lymphocytes, but our case presented initially with leukopenia. Further, her degree of transaminitis (levels > 10x) normal is usually restricted to the immunocompromised. Finally, EBV may also cause transient myo-or pericarditis as noted in select case reports. The mainstay of treatment is supportive, although steroids and acyclovir are used in cases of laryngeal edema, liver failure, or hemolytic anemia and thrombocytopenia. These agents have not been proven to reduce the length or severity of illness

Learning Objective #1: Appreciate hypertensive urgency as a potential late side effect of renal artery ablation (RAE) Learning Objective #2: Understand the importance of long-term blood pressure monitoring following renal artery ablation CASE: A 64-year-old year old woman with no personal or family history of hypertension was diagnosed with right renal angiomyolipoma incidentally on work up for latent TB and referred to interventional radiology for partial right RAE. On routine follow up one week post procedure, she was noted to be normotensive. One-month post procedure while receiving a screening mam-mogram, the patient was found to be hypertensive and was referred to the emergency room. On admission she was asymptomatic but found to have a systolic blood pressure in the 200s. Renal artery stenosis or dissection was ruled out via CT angiogram of the abdomen and renal angiography by inter-ventional radiology. No end organ complication was found. Serum renin was measured at 20, five times the upper limit of normal. Her blood pressure stabilized in the 130s with the initiation of amlodipine, and she was discharged the following day. IMPACT: Although rare, hypertensive urgency and emergency are potentially life-threatening complications of RAE. While patients typically do not receive long-term monitoring post procedure, this condition may present weeks fol-lowing embolization as evident in this case. With this in mind, patients require frequent and long-term blood pressure monitoring following RAE even in the absence of prior hypertension to prevent this potentially life-threatening complication. DISCUSSION: RAE can either be total or partial in cases when functional areas of the kidneys need to be spared. In patients receiving total RAE, the Juxtaglomerular apparatus (JGA) will likely be ablated as well, eliminating the initial step in the RAAS system and leaving the remaining kidney to compensate. Existing data regarding post procedural complications of RAE fail to demonstrate an increased risk of hypertension. Despite the lack of extensive evidence for this complication, there are several case reports suggesting that severe increases in blood pressure may occur, occasionally with fatal results. This seemingly paradoxical effect following a procedure that can be used in the treatment of hypertension is thought to be related to the degree to which the blood supply to the kidney is ablated. In patients that receive only partial embolization of the renal artery, the JGA may still be viable. Rarely, the residual JGA may increase RAAS activity in the setting of lower effective arterial blood volume. This mechanism is consistent with the increased renin activity noted in our patient. Blood pressure monitoring for weeks post embo-lization should be implemented to minimize the risk of hypertensive emergency in this patient population. This condition should also be included on the differential for any patient presenting with hypertension post RAE

LEARNING OBJECTIVE #1: Review existing and future therapeutic options for Adult Onset Still's Disease CASE: A 45-year-old Hispanic female presented with four weeks of highgrade fever and polyarthralgias, and one week of sore throat and night sweats. She visited an urgent care center and laboratory evaluation revealed white blood cell count 4.6K/uL with 48% bands and lactate dehydrogenase 953 U/L. Serum and urine protein electrophoresis revealed no monoclonal bands, and flow cytometry immunophenotypes were normal. Five days prior to presentation, she developed a pruritic rash on her arms and chest. Her condition failed to improve leading to her hospitalization. Her physical exam revealed a nonblanching erythematous maculopapular rash on her extremities, and pain with range of motion in her knees, ankles, elbows and wrists. Laboratory testing showed hemoglobin 11.2g/dL, erythrocyte sedimentation rate 67mm/hr, creactive protein 217mg/L and ferritin 4972ng/mL. Respiratory viral panel, quantiferon gold assay, HIV, parvovirus B19 IgM, CMV/EBV, antinuclear antibody and rheumatoid factor were unremarkable. Peripheral blood smears were negative for Plasmodium, Babesia, Trypanosoma and Microfilaria, as were serologies for Anaplasma, Ehrlichiosis, and Lyme. Whole body computed tomography scan was unrevealing. Skin biopsy showed neutrophilic urticarial dermatosis, and bone marrow aspirate revealed hypercellularity with trilineage hematopoiesis without evidence of lymphoma or leukemia. Given these findings, she was diagnosed with AdultOnset Still'sDisease and initiated on corticosteroids. Immunotherapy was considered, however she experienced symptom improvement. IMPACT: This case allowed us to explore the broad differential diagnosis for fever of unknown origin, forcing us to consider and ultimately exclude a range of pathologies - infectious, malignant, and rheumatologic - before arriving at this diagnosis of exclusion. DISCUSSION: Adult Onset Still's Disease (AOSD) is rare, with an estimated prevalence of 0.16-1 per 100,000 persons. Lacking a definitive diagnostic test, it is characterized by clinical and laboratory findings including fevers, arthralgias, rash and elevated ferritin. Corticosteroids have been the mainstay of treatment, with 76-95% of patients achieving symptom improvement and resolution of laboratory abnormalities. However, given complications of chronic steroid use, focus has shifted toward interventions on the cytokine cascade, including tumor necrosis factor-alpha (TNF- alpha), interleukin (IL)-1 and 6, thought to be a driver in AOSD. Research has shown that while serum TNF-alpha is increased in AOSD, TNF-alpha inhibitors offer little clinical benefit, thus shifting focus toward the interleukin response. In one study, the IL-1 receptor antagonist Anakinra resulted in defervescence and resolution of leukocytosis in 79% of subjects, compared to a 36% response with other biologics. IL-6 has also been studied as a treatment target, with Toclizumab showing improvement in arthritic symptoms