Case 1: Amyloid as a cause of refractory congestive heart failure
A 54-year-old woman with hypertension was admitted for evaluation of shortness of breath on exertion and paroxysmal nocturnal dyspnea for three months. She had recently been given a diagnosis of eosinophilic gastroenteritis after a colon biopsy revealed eosinophilic infiltration. Pulmonary exam was remarkable for rales. Laboratory testing revealed a peripheral eosinophilia. Chest radiograph demonstrated heart failure, and echocardiogram revealed moderate pericardial effusion with a normal ejection fraction. Workup for eosinophilia was initiated and revealed a positive Strongyloides IgG titer. Empiric treatments for Strongyloides and heart failure were started. Her symptoms improved and she was discharged home.
Despite appropriate outpatient treatment for heart failure, the patient was readmitted two months later with rapidly progressive heart failure and worsening pericardial effusion. Cardiac magnetic resonance imaging demonstrated pericardial nodularity and straightening of the interventricular septum, suggestive of constrictive pericarditis. A pericardial biopsy revealed chronic inflammation with occasional granulomas. The biopsies of the pericardium and the previous biopsies of the gastrointestinal tract were stained with Congo red stain and demonstrated apple-green birefringence under polarized light microscopy, consistent with amyloid light-chain (AL) amyloidosis. A bone marrow biopsy revealed multiple myeloma.
Systemic AL amyloidosis (primary amyloidosis) is a multi-organ systemic disease in which the amyloid protein consists of monoclonal light chains. AL amyloidosis may occur alone or in association with plasma-cell diseases such as multiple myeloma. Ninety percent of patients with AL amyloidosis have pathologic involvement of the heart; approximately 50% of those initially present with clinical features of heart failure. Cardiac AL amyloidosis often leads to rapidly progressing heart failure and should be considered in the setting of rapidly progressive symptoms. Clinically, amyloid heart disease may mimic constrictive pericarditis, coronary artery disease, valvular heart disease, and idiopathic hypertrophic or congestive cardiomyopathy. Although no single noninvasive test or abnormality is diagnostic of cardiac amyloid, reduced electrocardiographic voltages, in combination with echocardiographic evidence of left ventricular wall thickening, atrial dilation, and increased echogenicity (and less commonly thickened valves and a small pericardial effusion), make the diagnosis of amyloid more likely. Cardiac magnetic resonance imaging findings occur late in the disease and usually reveal late gadolinium enhancement of the myocardium.
- An infiltrative myocardial cardiomyopathy, such as amyloid, should be included early in the differential diagnosis of patients presenting with rapidly progressive heart failure.
Case 2: High-output heart failure from severe anemia
A 43-year-old woman with a history of menorrhagia and previously documented iron-deficiency anemia presented with three weeks of progressively worsening shortness of breath and lower-extremity swelling. On examination, she had a heart rate of 120 beats/min and conjunctival pallor. Her jugular venous pressure was elevated, and she had an enlarged, laterally displaced point of maximal impulse (PMI). Lower-extremity pitting edema extended up to her thighs bilaterally. Four-chamber dilatation was noted on echocardiography, with an ejection fraction of 60%. The initial hemoglobin was 2.5 g/dL (reference range for women, 12.3 to 15.3 g/dL), with a mean corpuscular volume of 47.2 fL/red cell (reference range, 80 to 96 fL/red cell). Results of iron studies revealed severe iron-deficiency anemia, with an iron level of 13 ng/mL (reference range, 65 to 175 ng/mL), total iron-binding capacity of 410 ng/mL (reference range, 250 to 410 ng/mL), percent iron saturation of 3% (reference range, 26% to 42%), and ferritin of 5 ng/mL (reference range, 10 to 150 ng/mL).
This patient has high-output heart failure due to severe iron-deficiency anemia. While patients with systolic or diastolic dysfunction usually have low or normal cardiac output, high output is defined by a cardiac index above the normal range of 2.5 to 4.0 L/min/m2. Conditions that can lead to high-output cardiac failure include sepsis, systemic arteriovenous fistulas, thyrotoxicosis, beriberi, multiple myeloma, obesity, pregnancy, carcinoid syndrome and anemia. Only in cases of severe anemia (hemoglobin <5 g/dL) does heart failure develop in the absence of underlying heart disease.
Although the mechanism of anemia-induced high-output heart failure is not completely understood, it is postulated that severe anemia results in a decrease in systemic vascular resistance through a release of renal and nitric oxide production. In addition, severe anemia results in a reduction in serum viscosity. This state of decreased vascular resistance leads to chronic activation of the sympathetic nervous system, renin-angiotensin-aldosterone axis and increased serum vasopressin. These hormonal derangements, along with chronic volume overload, gradually cause ventricular enlargement, remodeling and heart failure. Treatment should be aimed at the underlying condition rather than focus on typical heart failure medications. Our patient was carefully transfused to a hemoglobin of 8.2 g/dL and received diuresis with intravenous furosemide for symptom management. Four days after admission, she had clinically improved and was discharged home on oral iron supplements and scheduled for a gynecology follow-up to further evaluate her menorrhagia.
- High-output heart failure should be considered in the differential diagnosis of heart failure with preserved ejection fraction.
- Treating the underlying etiology is of utmost importance in high-output heart failure, as typical heart failure regimens will potentially worsen symptoms.
Case 3: Toxic liver injury from a mushroom omelet
A healthy 44-year-old woman presented with crampy abdominal pain, vomiting and watery diarrhea for one day as well as subjective fevers and myalgias. Her symptoms began 10 hours after eating an omelet made with mushrooms found in her backyard. Initially her vital signs were stable and examination revealed tenderness to palpation in the left lower quadrant of her abdomen. Initial laboratory and imaging evaluations were normal. Repeat laboratory studies are given in the Table.
The patient underwent rapid transplant evaluation for acute liver failure, and penicillin G and N-acetylcysteine infusions were started. Her course was complicated by recurrent diarrhea and lower gastrointestinal bleeding. Although the patient was listed urgently for a liver transplant, she made a full recovery with supportive care. The mushrooms the patient ingested were confirmed to be of the Amanita genus.
Amatoxin-containing mushrooms account for 90% of mushroom-related fatalities worldwide, with Amanita phalloides the most potent species. The presentation of Amanita mushroom toxicity mimics acute viral gastroenteritis and does not have any distinguishing characteristics or lab abnormalities. Approximately 6 to 24 hours following ingestion, patients typically develop a clinical gastroenteritis with normal liver function tests; 24 to 36 hours following ingestion, mild elevations in aspartate aminotransferase and alanine aminotransferase are usually detected. Two to four days afterward, hepatocyte death and disruption of hepatic venous and biliary flow occur, with dramatic elevations in aminotransferase levels and hyperbilirubinemia. Coagulopathy and encephalopathy may follow, and the patient may progress to multiorgan failure and death. Treatment is mostly supportive, but measures can be taken to decrease toxicity. Intravenous penicillin and silibinin block uptake of toxin into hepatocytes, and N-acetylcysteine limits damage from oxidative stress. Retrospective analysis of previous cases has suggested that an increased international normalized ratio and elevated serum creatinine three to four days after ingestion portend poor prognosis and may suggest the need for transplantation. This case highlights a classic presentation of Amanita poisoning and illustrates how early recognition with treatment and supportive care may prevent the need for a liver transplant.
- The initial presentation of acute mushroom toxicity is clinically indistinguishable from routinely encountered viral gastroenteritis.
- A high clinical suspicion for toxic liver injury, frequent laboratory monitoring, and a careful history are essential to the diagnosis of Amanita mushroom toxicity.
Case 4: Septic arthritis of the sternoclavicular joint
A 44-year-old man with diabetes presented with three weeks of progressively worsening pain at the base of his neck, associated with decreased range of motion in his left shoulder. He had consulted a clinician on two previous occasions and was prescribed ibuprofen, but the medication didn't provide relief. He reported no fever, cough, shortness of breath, weight loss or malaise. There was no history of trauma or intravenous drug use.
On presentation, the man's temperature was 101.1° Fahrenheit and there was a 3 cm × 3 cm mass overlying the left sternoclavicular joint, which was indurated, erythematous, warm and tender to palpation. Laboratory data revealed a white blood cell count of 8,000 cells/µL (reference range, 4,500 to 10,000 cells/µL), erythrocyte sedimentation rate of 104 mm/h (reference range, <15 mm/h), and C-reactive protein level of 92 mg/L (reference range, <5 mg/L). Blood cultures were negative, as were tests for HIV, gonorrhea and chlamydia.
Chest radiograph was unremarkable. MRI revealed classic signs of septic arthritis of the sternoclavicular joint, complicated by osteomyelitis of the manubrium and left clavicle with surrounding phlegmon. Culture of the joint aspirate grew Streptococcus pneumoniae. No vegetations were seen on transesophageal echocardiogram, and dental examination did not reveal any active infection in the oral cavity. He was successfully treated with six weeks of intravenous penicillin. No surgical debridement was needed. On follow-up, he recovered full function of the left upper extremity.
Septic arthritis of the sternoclavicular joint is a rare condition, accounting for 1% of all septic arthritis cases. It is usually seen in immunocompromised patients, especially those with diabetes or HIV, in addition to intravenous drug users. Patients usually present after a median of 14 days of symptoms, with complaints of chest, shoulder or neck pain and limited range of motion of the associated upper extremity. Fever and leukocytosis are present in 65% and 52%, respectively. Bacteremia is present in 62% of cases. Staphylococcus aureus is the most common etiologic agent (49%) while Streptococcus pneumoniae is quite rare (2%). MRI or CT scan of the chest is the most useful initial diagnostic study; sensitivities are 100% and 83%, respectively. Imaging also provides information about the extent of the disease and compromise of nearby structures. The definitive diagnosis is made by joint fluid culture.
Common serious complications include osteomyelitis (55%), phlegmon or abscess (25%) or mediastinitis (13%). More rare but serious complications include thrombosis of subclavian vein or superior vena cava. Early empiric parenteral antibiotic therapy with an antistaphylococcal penicillin is recommended. Surgical debridement may be necessary, especially in cases complicated with bone destruction, abscesses, mediastinitis or in those that do not respond to antibiotic therapy.
Case 5: Bilateral facial nerve palsy
A 44-year-old woman originally presented to the emergency department of an outside hospital with left-sided facial weakness. She was prescribed valacyclovir and prednisone for presumed Bell's palsy, which she took without improvement. She returned to the hospital complaining of myalgias and persistent left-sided facial weakness, as well as new right-sided facial weakness. On physical exam she was found to have bilateral facial nerve palsy, as well as left anterior cervical and submandibular lymphadenopathy.
Laboratory studies at that time revealed a leukocytosis with 58% atypical lymphocytes. Epstein-Barr virus (EBV) titers, including EBV early antigen, EBV IgM, EBV IgG, and EBV nuclear antigen IgG, were all positive. Lyme titers were negative and angiotensin-converting enzyme levels were normal. The patient was discharged with a presumed diagnosis of infectious mononucleosis.
She presented to our hospital one week later, complaining of continued myalgias and bilateral facial weakness. Physical exam was remarkable for bilateral facial nerve palsy as well as bilateral anterior cervical, submandibular, and posterior cervical lymphadenopathy. Laboratory studies revealed a white blood cell count of 55 × 103 cells/µL (reference range, 4.8 to 10.8 cells/µL) with 13% atypical lymphocytes, a calcium of 12.8 mg/dL (reference range, 8.5 to 10.5 mg/dL), and lactate dehydrogenase of 877 IU/L (reference range, 100 to 190 IU/L). Flow cytometry and bone marrow biopsy were consistent with adult T-cell leukemia/lymphoma. Western blot for human T-lymphotropic virus 1 (HTLV-1) was positive. The patient was treated with cytarabine and methotrexate. She was discharged from the hospital in remission.
Bilateral facial nerve palsy is an unusual finding with a limited differential diagnosis, including Lyme disease, Guillain-Barré syndrome, sarcoidosis, bacterial meningitis, syphilis, mononucleosis, skull fracture, and hematologic malignancy. Adult T-cell leukemia-lymphoma is a peripheral T-cell neoplasm associated with human T-lymphotropic virus 1 (HTLV-1) infection and typically presents with generalized lymphadenopathy, hepatosplenomegaly, immunosuppression, hypercalcemia (with or without lytic bone lesions), and/or skin lesions. Four variants have been described: acute, lymphomatous, chronic and smoldering. Facial nerve palsy is a rare presentation of non-Hodgkin's lymphoma. Also of note is the interpretation of EBV serologies. In this case, all EBV serologies, including EBNA IgG, were positive, which is not consistent with acute infection; the serologies are most consistent with an EBV infection that is outside of the acute phase and likely unrelated to the presentation and diagnosis of her new hematologic malignancy.
- Bilateral facial nerve palsy is an unusual finding with a limited differential diagnosis, among which hematologic malignancy must be considered.