A 63-year-old man presents to his physician due to persistent fevers. He says that he initially saw a physician for a fever about a month ago, and the workup was negative. He did not receive antibiotics at that time. Since then, he has measured his temperature at home and has had temperatures higher than 38.5°C. He denies any headache, cough, shortness of breath, abdominal pain, jaundice, bone or muscle pain, body swelling, or other concerning symptoms. He is otherwise healthy and sees the physician annually, receiving all necessary screening procedures. He has not traveled recently and has had no sick contacts or animal exposures. On physical examination, a new murmur is heard over the cardiac apex, but the rest of the examination, including assessment of skin and lymph nodes, is unremarkable. Three sets of blood cultures are sent to the laboratory and later return negative. An echocardiogram is performed and shows a vegetation on the mitral valve. Other significant laboratory values include a hemoglobin of 12.4 g/dL, a leukocyte count of 11,500/mm3 , and negative testing for ANA and antiphospholipid antibodies.
Which of the following is the likely cause of this patient’s recurring fevers?
Infective endocarditis. This patient meets the definition of fever of unknown origin (FUO), which requires recurring fevers >38.3°C for ≥3 weeks, with a failed attempt to make a diagnosis. Many cases remain undiagnosed; however, this patient has a new murmur on cardiac examination and a valvular vegetation on echocardiography. Though blood cultures are often positive in patients with endocarditis, there are certain organisms that can produce culture-negative infective endocarditis. Coxiella, Bartonella, and Streptococcus species are the most common causes. The HACEK organisms were previously thought to be the most common cause of culture-negative endocarditis; however, current blood culture techniques can isolate many of these organisms after 3 to 5 days.
A full workup for FUO includes many blood tests, urine studies, cultures from multiple sites, and imaging studies, but knowing the details of this workup is not high yield for the shelf examination. Just consider the main etiologic categories for FUO, and the details of the vignette usually indicate the diagnosis. (A) Malignancy is always a concern in a patient with FUO, with common examples including leukemia, lymphoma, renal cell carcinoma, and abdominal cancers. (B) Verrucous endocarditis (Libman–Sacks endocarditis) will also present with negative blood cultures and is usually asymptomatic; it is associated with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome; however, the negative tests for ANA and antiphospholipid antibodies rule out these diagnoses. (D) Vasculitides and other connective tissue diseases are causes of FUO, but these diagnoses are not suggested by the vignette. Though the clinical presentations vary considerably, findings that would suggest a vasculitis include palpable purpura, pulmonary and/or renal involvement, and asymmetric polyneuropathy. Other important causes of FUO include infections (e.g., TB, osteomyelitis, viral infections; always consider infections in HIV patients), thrombosis (e.g., deep venous thrombosis), and factitious fever.
A 54-year-old woman with a history of rheumatoid arthritis and hypertension presents to the Emergency Department with a high fever and headache. The symptoms began last night and were worse this morning. She also complains of severe sensitivity to light. Her medications include hydrochlorothiazide and methotrexate. She denies any cough, weight loss, chest pain, shortness of breath, or abdominal pain, and she has no history of chronic headaches or neurologic disease. Her temperature is 39.5°C, blood pressure is 146/90 mmHg, heart rate is 88 beats per minute, and respiratory rate is 14 breaths per minute. She is somewhat confused, and there is significant nuchal rigidity and her headache becomes worse when she moves her head quickly to the side. The neurologic examination, including a cranial nerve examination, is unremarkable. A funduscopic examination shows bilateral blurring of the optic disk margins and retinal venous engorgement.
Which of the following should be performed next in the workup of this patient?
CT scan. The suspected diagnosis here is meningitis, and a CT scan should be performed first to rule out mass effect before a lumbar puncture is performed. She has a high fever, as well as other symptoms/ signs of meningitis (including the most sensitive test for meningitis: the jolt accentuation sign, in which a patient’s headache intensifies after a quick head jolt). Kernig (pain and resistance with knee flexion while the hips are flexed at 90 degrees) and Brudzinski (involuntary flexion of hips and/or knees with passive neck flexion) signs are not sensitive, but they are fairly specific.
Once a diagnosis of meningitis is suspected and a lumbar puncture needs to be performed, a CT scan should be performed in patients thought to be at high risk for cerebral herniation. Risk factors include papilledema, previous CNS disease, a seizure in the past week, immunosuppression, altered mental status, and focal neurologic signs. (C) This patient has both papilledema and immunosuppression (methotrexate), and therefore, a CT scan should be performed before a lumbar puncture to assess the risk for cerebral herniation during lumbar puncture. (B) An MRI provides better visualization of the brain; however, it is costly and time-consuming. Because the purpose here is to rule out mass effect, a CT scan can do this adequately and quickly. (D) It is most appropriate to administer empiric antibiotics shortly after blood and CSF cultures are sent; however, the lumbar puncture has not been performed yet.
A 33-year-old woman presents with a chief complaint of abdominal pain. The pain is epigastric and is worse with meals. It is associated with nausea, a burning sensation, and bloating. She denies any weight loss, vomiting, and bloody or dark stools. She has no other medical problems and takes no medications. She denies recent NSAID use or heavy alcohol consumption. An upper endoscopy is performed, which shows several gastric ulcers and one duodenal ulcer. Biopsy confirms infection with Helicobacter pylori.
What is the most appropriate treatment at this time?
Amoxicillin, clarithromycin, and omeprazole. This patient presents with symptoms of dyspepsia and is found to have peptic ulcer disease (PUD) on endoscopy. Although there are other causes of gastric ulcers, H. pylori is the most common cause and should be treated when present. Triple therapy is the most common method of treatment and involves the use of clarithromycin, amoxicillin (an alternative is metronidazole), and a proton pump inhibitor for 10 to 14 days. (A) Metronidazole is an alternative to amoxicillin, so using both together without clarithromycin is not effective. (C) Quadruple therapy is unnecessary in most patients and should be used for resistant strains of H. pylori or if the patient is allergic to amoxicillin. (D) H. pylori eradication is the standard of care for PUD.
A 43-year-old woman presents to her physician for severe joint pain affecting her hands, elbows, and left knee. She has no other medical problems and works as a medical assistant at a local prison. On examination, the metacarpophalangeal joints of both hands are swollen and erythematous. Blood work reveals a positive rheumatoid factor. She elects to begin treatment with a disease-modifying antirheumatic drug (DMARD). Several weeks later, the patient has an improvement of the pain in her joints but now complains of fever, chills, and a productive cough. Her chest x-ray is shown in Figure below.
Which of the following represents the mechanism of action of this patient’s medication?
Binds and inhibits the effects of tumor necrosis factor-a (TNF-a). The patient’s chest x-ray is concerning for reactivation TB, which is indicated by the apical infiltrate with cavitation. Both her job as a healthcare worker and her exposure to jail inmates place her at risk for TB. Reactivation of latent TB is a known complication of TNF-α inhibitors used in the treatment of rheumatoid arthritis and other autoimmune diseases, and therefore the standard of care is to screen for latent TB before initiating one of these medications. TNF-α is released by activated macrophages and helps maintain the granuloma structure through signaling to surrounding lymphocytes. Agents that inhibit the actions of TNF-α include infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol. Although many of the other medications in the answer choices cause immunosuppression, which is a risk factor for reactivation of latent TB, the risk is much greater in TNF-α inhibitors and therefore B is the best answer. (A, C, D) These answer choices reflect the mechanisms of rituximab, methotrexate, and NSAIDs, respectively. Both rituximab and methotrexate are DMARDs.
A 32-year-old mailman presents to the Emergency Department with the development of fever and shortness of breath over the past day. He denies any sick contacts or abnormal exposures and was previously well with no past medical history. He is tachycardic and tachypneic, and a chest x-ray of his lungs shows mediastinal widening and bilateral pleural effusions.
Which of the following is the most likely responsible organism?
Bacillus anthracis. The acute onset of a pulmonary syndrome with mediastinal widening and pleural effusions is concerning for a bioterrorism agent, and B. anthracis is the most likely organism responsible. The CDC lists anthrax as a very likely bioterrorism agent to be used given its very high mortality rate, ease of use, and durability of the spores. It can be released in the mail (as was done in 2001, killing 5), or released into the food, water, or air (e.g., cropduster planes). Infection is indicated by the affected system (pulmonary, GI, and cutaneous anthrax), and pulmonary anthrax has the highest mortality.
(Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae) may cause CAP, but would not show mediastinal widening on chest x-ray. Pseudomonas s aeruginosa is a common cause of HAP. C. botulinum can cause a severe flaccid paralysis, and C. perfringens can cause both food poisoning and gas gangrene. (Legionella pneumophila, Influenza virus, Yersinia pestis, Francisella tularensis, and Coxiella burnetii)These are potential bioterrorism agents that cause respiratory symptoms; however, mediastinal widening is consistent with anthrax and not these other infections. Legionella causes Legionnaires’ disease (or the less severe Pontiac fever), which presents with symptoms of pneumonia, confusion, relative bradycardia (low for what the heart rate should be in the presence of fever), hyponatremia, and renal/hepatic abnormalities on laboratory values. Influenza causes significant morbidity and mortality in those at risk (e.g., immunosuppressed, elderly), and will show bilateral interstitial or alveolar infiltrates if it affects the lungs. Yersinia pestis causes the bubonic plague, which presents with sudden painful lymphadenopathy and bilateral infiltrates in the cause of pneumonic plague. F. tularensis causes tularemia, which can present in different ways based on the infected system. If the lungs are infected, it can produce hemorrhagic inflammation with bilateral infiltrates and hilar adenopathy on chest x-ray. C. burnetii causes Q fever, which presents not only with mild respiratory symptoms (i.e., nonproductive cough) but also with high fever, headache, myalgias, vomiting, diarrhea, abdominal pain, and/or chest pain.
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