Case 1: E-cigarette or vaping product use-associated lung injury
By Robert W. Kirchoff, MD, ACP Member; Jack McHugh, MBBCh, ACP Resident/Fellow Member; Rahul Chaudhary, MBBS, FACP; and Dennis M. Manning, MD, FACP
A 33-year-old man with a history of cannabis use and bipolar I disorder presented with a one-week history of a cough productive of “foamy” sputum, malaise, and fatigue. He did not report any gastrointestinal symptoms but did report intermittent use of marijuana via a vaping pen. Upon admission, the patient was noted to be febrile (39 °C) and tachycardic (heart rate, 109 beats/min) with an oxygen saturation of 91% on room air. Respiratory exam was notable for diminished air entry bilaterally. Chest X-ray showed perihilar interstitial and alveolar airspace opacities (Figure 1). Laboratory studies were notable for leukocytosis (white cell count, 10.1 × 109 cells/L; reference range, 3.4 to 9.6 × 109 cells/L). Blood cultures, influenza test, and respiratory viral panel were negative. Urine drug screen was positive for tetrahydrocannabinol (THC).
The patient was admitted for hypoxia and treated empirically for community-acquired pneumonia with ceftriaxone and azithromycin. He was observed for two days with improvement in symptoms and discharged on a course of cefdinir. He was counseled on cessation of vaping products. He was seen for outpatient follow-up one week after discharge, at which time he continued to do well and reported no residual symptoms.
The diagnosis is e-cigarette or vaping product use-associated lung injury (EVALI). This is an emerging public health issue in the United States; as of Jan. 7, 2020, 2,558 hospitalizations for EVALI had been reported, with 60 fatalities. Respiratory symptoms including pleuritic chest pain, cough, and congestion have been reported in 96% of patients. Gastrointestinal symptoms including abdominal pain, diarrhea, nausea, and vomiting have been reported in 80% of patients in the largest case series to date, published by the New England Journal of Medicine on April 23. Aerosolized vaping products containing THC (colloquially referred to as “dank vapes”) were implicated in 80% of cases in this series. Chest radiography should be performed in all patients when EVALI is suspected. The characteristic finding on chest X-ray is bilateral pulmonary infiltrates. Abnormal laboratory tests that have been reported in EVALI patients include elevations in white blood cell count, erythrocyte sedimentation rate, and C-reactive protein; aminotransferase levels may also be elevated in up to half of patients. Other testing should include screening for COVID-19, influenza, and other respiratory viruses. In severely ill patients, a standard work-up for severe community-acquired pneumonia should be done, along with chest CT and consultation with pulmonology for consideration of bronchoscopy.
Admission should be strongly considered in patients with decreased oxygen saturation (<95%) or respiratory distress. Obesity has been associated with worse outcomes, and obese patients should be considered at high risk for severe disease. Given that the symptoms often overlap with those of community-acquired pneumonia, empiric antibiotics should be initiated per local guidelines. In a recent case series published by the New England Journal of Medicine on March 5, approximately half of the patients had respiratory improvement after glucocorticoid treatment. Glucocorticoids should be considered if the patient does not improve in the first 48 hours or if symptoms worsen following admission. All patients should receive counseling regarding cessation of vaping products, with referral to addiction services if available and if patients agree. Hospitals should notify public health when a patient is hospitalized for EVALI, since this information has been requested by the CDC.
- EVALI should be considered in patients presenting with a history of vaping and respiratory and gastrointestinal symptoms with bilateral infiltrates on chest imaging.
- Glucocorticoids may be helpful in management, and aggressive treatment with empiric antimicrobial therapy should be pursued given the overlapping presentation of bacterial pneumonia.
Drs. Kirchoff and McHugh are co-primary authors of this case. All of the authors are affiliated with Mayo Clinic in Rochester, Minn.
Case 2: Early repolarization pattern in an athlete
By Magued W. Haroun, MD, ACP Resident/Fellow Member; Vladyslav Dieiev, MD, ACP Member; Pakhi Goel, MD, ACP Resident/Fellow Member; and Kristin A. Swedish, MD, MPH, ACP Member
A 40-year-old man with no significant medical history presented with two episodes of palpitations. He was an athlete who had run three marathons during the preceding two weeks. Palpitations were nonexertional, lasted for 10 minutes, and had resolved by the time of presentation. He did not have chest pain, shortness of breath, presyncope, or syncope. Physical examination was unremarkable.
An initial electrocardiogram (EKG) (Figure 2) revealed ST-segment elevation as well as end-QRS slurring in leads V3 and V4 of 2 mm in height, end-QRS notching in lead I, and aVL and T-wave inversions in leads III, V3, and V4 that resolved on the second day of admission (Figure 3). There were no ST depressions in reciprocal leads. Serial levels of troponin T were persistently less than 0.01 ng/mL (reference range, <0.10 ng/mL). Laboratory workup was otherwise unremarkable. The patient remained asymptomatic throughout the admission. Telemetry throughout the admission was not significant for arrhythmias. Echocardiography revealed normal left ventricular size and wall motion. Ejection fraction was estimated at 55%. Coronary angiography and left-heart catheterization revealed patent coronary arteries.
The diagnosis is anterolateral early repolarization pattern (ERP) likely induced by intense physical exercise. ST-segment elevation is a worrisome clinical finding that raises suspicion for an acute coronary process, but it is important to consider these findings in clinical context and to use specific EKG criteria for diagnosis. In our case, the EKG pattern and morphology and lack of chest pain, electrolyte disturbances, or troponin elevation were consistent with ERP in anterolateral leads. Imaging and invasive evaluation confirmed absence of any underlying disease process that could have caused the signs and symptoms. Other differential diagnoses for ST-segment elevation include pericarditis, QRS complex abnormalities, hyperkalemia, and Brugada syndrome. This patient didn't meet the clinical, electrocardiographic, or laboratory criteria for any of these diagnoses.
ERP is characterized by J-point ST-segment elevation and manifests either as terminal QRS slurring (the transition from the QRS segment to the ST segment) or notching (a positive deflection inscribed on the terminal QRS complex) associated with concave upward ST-segment elevation and prominent T waves in at least two contiguous leads. While ERP has always been considered a normal EKG variant, some studies have suggested an association between inferolateral ERP and increased risk of ventricular arrhythmias. This understanding has led to classifying anterolateral ERP as benign early repolarization and inferolateral ERP as malignant early repolarization.
Prevalence of ERP in the general population ranges from 3% to 13%, whereas estimated prevalence in athletes ranges from 10% to 90%. Prevalence has been shown to increase after intense physical training, especially endurance training including rowing or marathon running. ERP is not associated with structural left ventricular measurement, including chamber volume or wall thickness, both of which are well-established components of the “athlete heart.” This suggests that exercise-related ERP may be an isolated electric phenomenon that develops parallel to, but not as a result of, structural myocardial remodeling.
- While ST-segment elevation may reflect occlusion of the coronary artery and ongoing necrosis of the myocardium, other causes should be considered.
- ERP is characterized by specific EKG findings and is more common among athletes than the general population.
The authors are affiliated with the department of medicine at Montefiore Medical Center in Bronx, N.Y.
Case 3: Klebsiella pneumoniae liver abscesses
By Munder Abuaisha, MD, ACP Resident/Fellow Member; Noura Semreen, MD, ACP Resident/Fellow Member; Razan Elsayed, MD; and Sofia Terner, MD, ACP Member
A 64-year-old Korean-American man with a medical history of type 2 diabetes with poor glycemic control presented with a fever of 40.6 °C and chills. His heart rate was 124 beats/min with a systolic blood pressure of 110 mm Hg. The physical examination was unremarkable apart from mild nontender hepatomegaly. A CT scan of the abdomen and pelvis showed multiple bilobar multifocal liver abscesses (Figure 4) along with a right lower-pole renal abscess. An MRI of the abdomen confirmed kidney abscesses (Figure 5). The largest hepatic abscess was aspirated under CT guidance, confirming the finding of a metastatic Klebsiella pneumoniae abscess in the context of mildly elevated liver enzymes (aspartate aminotransferase level, 57 U/L [reference range, 10 to 40 U/L]; alanine aminotransferase level, 86 U/L [reference range, 7 to 56 U/L]; alkaline phosphatase level, 407 U/L [reference range, 20 to 140 U/L]; total bilirubin level, 1.7 mg/dL [reference range, 0.1 to 1.2 mg/dL]; conjugated bilirubin level, 1.3 mg/dL [reference range, <0.3 mg/dL]). Two sets of blood cultures grew multisensitive Klebsiella pneumoniae. Urine cultures also grew Klebsiella pneumoniae (>100,000 colony-forming units/mL) with a similar sensitivity panel as the blood cultures. The patient was treated with ceftriaxone, resulting in resolution of symptoms, after which he was discharged home. Serial CT scans over two months from the beginning of treatment showed near-complete resolution of the hepatic and renal foci.
The patient's diagnosis is community-acquired Klebsiella pneumoniae primary liver abscess (KLA). This is a rare condition that usually presents with a single liver abscess and unilobar involvement in the absence of hepatobiliary disease. It is an emerging infection worldwide with predominance in Southeast Asia. Diabetes or impaired fasting glucose is present in most patients and is the most common known risk factor for KLA. The mechanism by which diabetes predisposes patients to KLA is not entirely understood. Diagnosis is made based on radiography and is confirmed with cultures. Percutaneous drainage guided by imaging is used for both diagnosis and treatment, and when coupled with the appropriate antibiotic regimen, there is a cure rate of 76%. The antibiotic regimen should be determined based on the sensitivity of the abscess isolates; usually, isolates remain sensitive to cephalosporins, and resistant strains have been rarely reported. Although KLA was once considered fatal, the prognosis is now excellent, and significant morbidity due to KLA usually occurs only in patients with severe underlying disease and metastatic complications.
- Community-acquired KLA is a rare emerging condition and requires a high index of suspicion, as early detection is key to successful treatment and prevention of invasive syndrome with metastatic infection.
- Percutaneous drainage guided by imaging is used for both diagnosis and treatment of KLA and must be coupled with the appropriate antibiotic regimen.
The authors are affiliated with Englewood Hospital and Medical Center in Englewood, N.J.
Case 4: Takayasu arteritis
By Daniel T. Mulcahy, DO, ACP Member
A 26-year-old woman went to the ED for symptomatic anemia with a hemoglobin level of 7.2 g/dL (reference range, 11.5 to 14.5 g/dL). She reported unintentional weight loss of 20 lb over a few months, daily fevers for one month, night sweats two or three times a week, a dry cough, and increasing fatigue and exertional dyspnea. There was no history of melena, and her menstrual periods were typically light. History included chronic thoracic back pain, antiphospholipid syndrome, hypertension, and a negative colonoscopy six months prior for rectal bleeding.
Vital signs in the ED were normal. The patient's BMI was 18 kg/m2. She exhibited pallor but was in no acute distress. Rectal exam was heme negative and had no other significant physical findings. Labs at admission were notable for a hemoglobin level of 7.4 g/dL, a mean corpuscular volume of 60 fL (reference range, 80 to 100 fL), a platelet count of 708,000 cells/μL (reference range, 140,000 to 350,000 cells/μL), an iron level of 10 μg/dL (reference range, 40 to 190 μg/dL), total iron-binding capacity of 199 μg/dL (reference range, 250 to 450 μg/dL), a ferritin level of 238 ng/mL (reference range, 10 to 120 ng/mL), a C-reactive protein (CRP) level of 103 mg/L (reference range, <8 mg/L), and an erythrocyte sedimentation rate (ESR) of 127 mm/h (reference range, 0 to 20 mm/h).
Additional infectious and rheumatologic lab testing, including antinuclear antibody, rheumatoid factor, serum and urine protein electrophoresis, celiac panel, HIV, thyroid-stimulating hormone, and tuberculosis test, were negative. Blood cultures were negative. A CT scan of the abdomen showed possible irregularity and narrowing at the superior mesenteric artery (SMA). A subsequent CT angiogram of the abdomen and pelvis showed circumferential thickening of the proximal abdominal aorta, irregularity of the celiac artery trunk, and diffuse thickening of the origin and proximal SMA (Figure 6). The patient was treated with IV methylprednisolone, 40 mg twice daily, for Takayasu arteritis and then transitioned to prednisone, 60 mg/d, for prolonged outpatient taper over several months once the disease stabilized and her inflammatory markers normalized. Initiation of azathioprine, which has lower fetal teratogenic risk than methotrexate, was planned for steroid-sparing purposes, since the patient had interest in having additional children.
The diagnosis is Takayasu arteritis, a rare (2 to 3 cases per million persons per year in the U.S.), systemic, inflammatory large-vessel vasculitis of unknown cause that typically affects women of childbearing age. There is a 9:1 female predominance, and the disease appears to occur more often in Asian women. Symptoms may include limb claudication with exertion, chest pain, headache, and systemic symptoms of weight loss, fatigue, fevers, and arthralgias or myalgias. Examination commonly reveals vascular bruits (80%), often multiple, in the carotid, subclavian, and abdominal vasculature, diminished or absent pulses associated with limb claudication, blood pressure discrepancy between the right and left sides, and hypertension often reflecting renal artery stenosis. Additional findings may include aortic regurgitation murmur if there is aortic root dilatation, retinopathy, and neurologic features due to hypertension and/or ischemia.
Laboratory findings are nonspecific but typically reflect inflammation, such as elevated ESR and CRP level, thrombocytosis, and normocytic anemia. Diagnosis according to the American College of Rheumatology requires three of six criteria: age 40 years or younger at onset, claudication of the extremities, decreased pulsation of one or both brachial arteries, systolic blood pressure difference of 10 mm Hg or more between the arms, bruit of one or both subclavian arteries or aorta, arteriographic narrowing/occlusion of the aorta or its primary branches, or large arteries in the extremities not due to other causes. Fluorodeoxyglucose-positron emission tomography has been shown to be useful in diagnosis and possibly monitoring disease activity.
Treatment is glucocorticoids tapered over weeks to months to suppress vascular inflammation and manage symptoms. An adjunctive steroid-sparing immunosuppressive agent such as methotrexate or azathioprine is required in most patients to minimize steroid-related complications and control disease progression. Immunosuppressive agents such as tumor necrosis factor-alpha and IL-6 receptor inhibitors have been used when patients do not achieve or maintain remission. Surgical or percutaneous revascularization procedures may be required in patients with certain conditions, including renovascular hypertension, coronary stenosis with ischemia, cerebral ischemia, thoracic/abdominal aortic aneurysms, severe coarctation of the aorta, significant aortic regurgitation, and claudication induced by routine activity. Low-dose aspirin should be considered to prevent ischemic complications.
During treatment and follow-up with a rheumatologist, disease activity should be evaluated by symptoms, inflammatory markers, and repeat vascular imaging studies. Complications are mainly due to arterial occlusion and related damage, including limb ischemia, stroke/transient ischemic attack, renal failure, and hypertension. Approximately 20% of patients have a monophasic illness and self-limited disease. The remaining 80% have a progressive or relapsing/remitting disease course. The overall 10-year survival rate is 90% but declines with the number of major complications experienced.
- Takayasu arteritis is a rare, large-vessel vasculitis with a 9:1 predominance among women, usually presenting in those younger than age 40 years.
- This condition most often presents with limb claudication with exertion, chest pain, headache, and systemic symptoms of weight loss, fatigue, fevers, and arthralgias or myalgias.
Dr. Mulcahy is affiliated with Lehigh Valley Health Network-Muhlenberg in Bethlehem, Pa.