Case 1: Infective endocarditis presenting with stroke
By Stephen Huynh, BA, and Michael Yoo, MD, FACP
An 80-year-old man with a history of anemia, right total knee replacement six years before admission, and mild aortic stenosis presented with left-sided vision loss for several minutes. He reported fatigue, anorexia, and weight loss for the past two months, but no palpitations or previous episodes of vision loss. Vital signs were normal. Physical examination was notable for a III/VI crescendo-decrescendo systolic murmur appreciated at the right upper sternal border. His right knee was swollen compared to the left. The remainder of his exam was normal, and there were no cutaneous stigmata of infective endocarditis. Laboratory evaluation revealed a microcytic anemia. A head CT was negative for stroke. The patient was admitted to our institution to evaluate for occult atrial fibrillation.
An MRI of the brain subsequently revealed acute infarction of the corpus callosum, along with multiple scattered punctate infarcts throughout the brain (Figure 1). Doppler ultrasonography was negative for significant carotid stenosis. Telemetry during hospitalization did not detect atrial fibrillation. A transthoracic echocardiogram revealed an aortic valve vegetation. A knee arthrocentesis was performed, and blood cultures were drawn from multiple sites. Empiric intravenous vancomycin was initiated, and washout of the right knee was performed by orthopedic surgery. Blood, urine, and synovial fluid cultures were all ultimately positive for Enterococcus faecalis.
The patient was treated with intravenous ampicillin and ceftriaxone with clinical improvement during his hospitalization but had another cardioembolic event for which he underwent aortic valve replacement two months later. He did well from a neurological standpoint with no persistent deficits.
The incidence of infective endocarditis is approximately 15 cases per 100,000 in the United States. An estimated three-fourths of patients with infective endocarditis have underlying structural heart disease, and 12% to 30% of patients have aortic valve disease. Symptomatic brain embolization is estimated to occur in up to one-third of infective endocarditis cases, while up to 80% of patients may have evidence of stroke on MRI. In one study of patients with left-sided infective endocarditis, incidence of stroke fell from 4.8 to 1.7 per 1,000 patient-days between the first to second weeks of antibiotic therapy.
Infective endocarditis can be difficult to diagnose, with a wide array of presenting clinical signs and symptoms, along with other conditions to consider. The modified Duke criteria can help distinguish infective endocarditis from other diseases included on the differential diagnosis. The major Duke criteria are positive blood cultures from two separate sites and endocardial involvement as demonstrated by vegetations on echocardiogram, or a new murmur of valvular insufficiency. Minor Duke criteria include fever, immunologic phenomena, vascular phenomena, risk factors, and microbiologic evidence of infection. Our patient presented with embolic stroke, anemia, murmur, malaise, anorexia, and weight loss, all of which can be seen in infective endocarditis. The index of suspicion must be high, and a thorough history and physical exam should be performed with concurrent blood cultures and echocardiography.
- Infective endocarditis is an important diagnostic consideration in patients presenting with embolic stroke or transient ischemic attack, especially if accompanied by symptoms such as fatigue, anorexia, and weight loss.
- Antibiotic treatment for infective endocarditis significantly reduces the risk of stroke in the first two weeks of therapy.
Case 2: Milk-alkali syndrome
By Jason Andrade, MS, and Michael Yoo, MD, FACP
A 51-year-old woman with hypertension, esophagitis, and remote vertical banded gastroplasty presented with four days of vomiting. She had a single episode of hematemesis and multiple other symptoms: abdominal pain, constipation, dysphagia, fatigue, aches, dysarthria, and ataxia. Her medications included hydrochlorothiazide, ranitidine, and over-the-counter calcium carbonate. Physical examination revealed mild epigastric tenderness. Her complete blood count was significant for leukocytosis. Her chemistries revealed acute kidney injury, metabolic alkalosis, and a markedly elevated calcium level (21.7 mg/dL, reference range 8.5-10.2 mg/dL). Her parathyroid hormone (PTH) level was undetectable, while her phosphorus, 25-OH vitamin D, and PTH-related protein levels were within reference ranges. Her serum protein electrophoresis panel (SPEP) demonstrated monoclonal gammopathy of undetermined significance. Her head CT was negative, and upper endoscopy revealed esophagitis.
A urinalysis demonstrated pyuria and hematuria, and a follow-up retroperitoneal ultrasound revealed nonobstructing kidney stones. An abdominal X-ray revealed extensive radiopaque material throughout the colon, despite the absence of oral contrast (Figure 2). Further history revealed excessive antacid consumption (more than 20 tablets daily). The radiographic findings were consistent with colonic calcium deposits. Calcium supplementation and hydrochlorothiazide were discontinued, intravenous fluids were given, and the patient's hypercalcemia and related symptoms resolved. She was administered polyethylene glycol, enemas, and manual disimpaction to relieve the calcium deposits in her colon. She was discharged home on pantoprazole and amlodipine.
Milk-alkali syndrome was rarely seen in the United States prior to the 1990s, accounting for 2% of hospital admissions for hypercalcemia. Since then, with greater emphasis on calcium supplementation for osteoporosis and easier availability of over-the-counter antacids such as calcium carbonate, hospitalizations due to milk-alkali syndrome have risen significantly. Milk-alkali syndrome became, and has remained, the third most common cause of hypercalcemia in hospitalized patients in the United States, accounting for approximately 12% of hypercalcemia admissions.
Calcium intake is generally well tolerated with normal renal function and appropriate vitamin D suppressive capabilities. However, when calcium is ingested in amounts greater than 10 grams daily, compensatory mechanisms are overwhelmed and excess calcium is absorbed into the bloodstream. The diagnosis of milk-alkali syndrome is made by a history of calcium ingestion and exclusion of other causes of hypercalcemia. It is characterized by the triad of hypercalcemia, metabolic alkalosis, and acute kidney injury. PTH is not elevated. Extreme cases may be apparent on imaging—the impaction of calcium carbonate within the colon gives the appearance of contrast enhancement. As in our patient, it is important to consider the effect of thiazide diuretics on hypercalcemia. Malignancy must also be considered in cases of severe hypercalcemia, and testing such as SPEP, imaging, or biopsy should be performed as clinically indicated.
- The increasing prevalence of milk-alkali syndrome makes it an important cause to consider in hospitalized patients presenting with hypercalcemia.
- The use of over-the-counter medications, and calcium supplements in particular, should be carefully reviewed when taking the history of a patient being admitted with hypercalcemia.
Case 3: Multiple myeloma as an incidental finding
By Wendy Zhou, BA, and Michael Yoo, MD, FACP
A 52-year-old man presented with confusion and weakness. He fell three weeks before presentation, resulting in right chest wall pain for which he took daily ibuprofen. Vital signs were normal. Physical examination revealed tenderness along the right costal margin and egophony of the left upper lung field. Laboratory studies revealed leukocytosis, anemia, and thrombocytopenia. Chest CT was remarkable for a left upper lobe infiltrate and healing fractures of the right sixth and seventh ribs. The patient was started on levofloxacin for pneumonia and transfused 2 units of packed red blood cells. He underwent upper endoscopy, which revealed gastritis with ulcerations, presumed secondary to ibuprofen use. A proton-pump inhibitor was started, and his hemoglobin level stabilized after transfusion.
Incidentally, a phlebotomist noted that hyperviscosity in the patient's blood, and a laboratory technician noted rouleaux formation of erythrocytes (Figure 3). An SPEP revealed an elevated M-band and total protein level. Additional labs revealed significantly elevated beta-2-microglobulin and IgG levels. Given the findings of monoclonal gammopathy with associated hyperviscosity, the patient underwent a bone marrow biopsy that confirmed a diagnosis of multiple myeloma. The patient underwent several rounds of plasmapheresis during his hospitalization and was referred for outpatient hematology management upon discharge.
Multiple myeloma is a hematologic cancer of plasma cells, leukocytes that produce antibodies and play a significant role in immune function. In multiple myeloma, healthy plasma cells undergo uncontrolled proliferation and production of abnormal antibodies. Monoclonal myeloma cells produce large quantities of the same antibody (e.g., IgG or IgM), resulting in the hallmark characteristic “M spike” on serum protein electrophoresis. The increased production of abnormal antibodies from these monoclonal myeloma cells prevents and suppresses normal plasma cells from producing antibodies; excessive production of abnormal antibodies may also result in hyperviscosity, as in our patient. Further, the antibodies prevent production of other cells in the bone marrow: red blood cells, platelets, and white blood cells. As a result, patients may develop anemia, excessive bleeding, and infections. Kidney failure is often seen due to cast nephropathy, tubular obstruction from immunoglobulin deposition due to the kidneys' attempt to filter and excrete the excess proteins.
Patients may experience bone pain due to the effect of increased osteoclast activity. The resultant bone lesions are lytic due to increased bone resorption and commonly involve the ribs and spine. However, only 60% of patients present with focal lytic lesions on radiographs at the time of diagnosis.
- Hyperviscosity and rouleaux formation noted on laboratory testing can suggest an underlying paraproteinemia, especially when present with suggestive clinical findings.
- Lytic bone lesions are important diagnostic findings in multiple myeloma but are present on radiographs at the time of diagnosis in only 60% of patients.