The following cases and commentary, which focus on pregnancy, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 18).
Case 1: Pneumonia in pregnancy
A 25-year-old woman is hospitalized with a 4-day history of fever and cough productive of brown sputum. She is at 14 weeks' gestation with her first pregnancy. Medical history is significant for mild persistent asthma. Medications are an albuterol inhaler, beclomethasone inhaler, and a prenatal vitamin.
On physical examination, temperature is 38.2 °C (100.8 °F), blood pressure is normal, pulse rate is 122/min, and respiration rate is 24/min. Oxygen saturation is 94% breathing ambient air. Crackles are heard at the left lung base on pulmonary auscultation.
Chest radiograph shows a left lower lobe infiltrate.
Which of the following is the most likely cause of pneumonia in this patient?
A. Escherichia coli
B. Klebsiella pneumoniae
C. Listeria monocytogenes
D. Staphylococcus aureus
E. Streptococcus pneumoniae
Case 2: Low serum sodium
A 25-year-old woman is evaluated in the emergency department for chest pain after a belted motor vehicle accident. She is pregnant at approximately 23 weeks' gestation. She reports no additional symptoms and is otherwise well. Her only medication is a prenatal vitamin.
On physical examination, the patient is afebrile, blood pressure is 102/62 mm Hg, and pulse rate is 80/min. Pain and bruising over the left chest wall are noted. Abdominal examination findings are consistent with changes of pregnancy.
Laboratory studies are significant for a serum sodium level of 132 mEq/L (132 mmol/L).
Which of the following is the most likely cause of this patient's low serum sodium level?
A. Excessive water intake
B. Hypotension-induced antidiuretic hormone release
C. Normal physiologic change in pregnancy
D. Syndrome of inappropriate antidiuretic hormone secretion
Case 3: Cough and dyspnea
A 39-year-old woman is evaluated for new-onset nonproductive cough and dyspnea on exertion. She is pregnant at 32 weeks' gestation. Medical history is unremarkable. Her only medication is a prenatal vitamin.
On physical examination, temperature is 37.0 °C (98.6 °F), blood pressure is 105/62 mm Hg, pulse rate is 100/min, and respiration rate is 22/min. Oxygen saturation is 86% breathing ambient air. Cardiopulmonary examination is normal. She has a gravid uterus and 1+ edema of the lower extremities without calf tenderness.
Laboratory studies show hemoglobin 12.1 g/dL (121 g/L), leukocyte count 4800/µL (4.8 × 109/L), and platelet count 189,000/µL (189 × 109/L). Urinalysis is normal.
Doppler ultrasonography of both legs is negative for deep venous thrombosis.
Which of the following is the most appropriate diagnostic test to perform next?
A. CT angiography
B. D-dimer assay
C. Magnetic resonance pulmonary angiography
D. Pulmonary function testing
E. Ventilation-perfusion lung scan
Case 4: Fever after travel
A 27-year-old woman is hospitalized with a 5-day history of intermittent fever, headache, muscle pains, and abdominal cramps. She returned 8 days ago from a 1-week trip to Kenya and Tanzania. She spent time outdoors in the evening and went hiking in a wooded park. She is pregnant at 20 weeks' gestation. She declined pretravel immunizations as well as antimalarial chemoprophylaxis. Her only medication is a prenatal vitamin.
On physical examination, temperature is 39.1 °C (102.3 °F), blood pressure is 98/64 mm Hg, pulse rate is 112/min, and respiration rate is 16/min. Her conjunctivae are icteric.
Cardiopulmonary examination reveals regular tachycardia. The remainder of the examination is unremarkable.
A peripheral blood smear is shown.
Which of the following is the most likely causative agent?
A. Plasmodium falciparum
B. Plasmodium knowlesi
C. Plasmodium malariae
D. Plasmodium ovale
E. Plasmodium vivax
Case 5: Syncope
A 24-year-old woman is evaluated for an episode of syncope. She is in her sixth month of pregnancy. She reports exertional dyspnea and occasional chest pain. She has sickle cell disease characterized by acute pain events occurring four to five times per year, typically not requiring hospitalization. She had an episode of acute chest syndrome 1 year ago, at which time she received exchange transfusion. Medications are a prenatal multivitamin and folic acid supplement.
On physical examination, temperature is 37 °C (98.7 °F), blood pressure is 90/60 mm Hg, pulse rate is 110/min, and respiration rate is 20/min. Oxygen saturation is 98% breathing ambient air. Cardiac examination reveals a parasternal heave. The pulmonic component of the S2 is accentuated, and a holosystolic murmur that increases with inspiration is heard at the apex. Other examination findings are normal.
Electrocardiography reveals right axis deviation, a tall R wave in lead V1, and inverted T waves in V1 to V3.
Laboratory studies show hemoglobin 8.2 g/dL (82 g/L), leukocyte count 13,600/µL (13.6 × 109/L), platelet count 385,000/µL (385 × 109/L), and reticulocyte count 7% of erythrocytes.
Which of the following is the most appropriate diagnostic test to perform next?
A. Cardiac MRI
C. Exercise stress test
D. Thoracic aortography
Case 6: Severe headache
A 36-year-old woman is evaluated for a severe headache. She is at 36 weeks' gestation with her first pregnancy. Her only medication is a prenatal vitamin.
On physical examination, temperature is 37.0 °C (98.7 °F), blood pressure is 160/100 mm Hg, pulse rate is 100/min, and respiration rate is 16/min. Oxygen saturation is 98% breathing ambient air. Neurologic examination is nonfocal. Cardiopulmonary examination is normal. She has a gravid uterus and 2+ edema of the lower extremities. No petechiae or ecchymoses are seen.
Laboratory studies show hemoglobin 11.9 g/dL (119 g/L), leukocyte count 12,700/µL (12.7 × 109/L), platelet count 52,000/µL (52 × 109/L), alanine aminotransferase 50 U/L, aspartate aminotransferase 52 U/L, creatinine 1.2 mg/dL (106 µmol/L). Urinalysis shows 3+ proteinuria.
The peripheral smear shows occasional fragmented erythrocytes without platelet clumping.
Which of the following is the most appropriate management?
B. Emergent delivery
C. High-dose dexamethasone
D. Plasma exchange
Answers and commentary
Correct answer: E. Streptococcus pneumoniae.
Streptococcus pneumoniae is the most likely cause of this patient's community-acquired pneumonia (CAP). Pneumonia is the most common cause of fatal nonobstetric infection in pregnancy. The microbiology of CAP in pregnancy is similar to that seen in the general population. Among patients requiring hospitalization, the most common pathogens are S. pneumoniae, Haemophilus influenzae, and atypical organisms, including Legionella species, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Empiric treatment of pregnant patients is similar to that in nonpregnant adults, although quinolones and tetracyclines are relatively contraindicated because of the potential for teratogenic effects. In addition to these common bacterial causes of CAP, pregnant women are at increased risk for serious viral pneumonia from influenza virus and varicella-zoster virus, so it is recommended that pregnant women receive seasonal influenza vaccination.
Gram-negative bacteria, including Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter species, Escherichia coli, and Enterobacter species, are rarely implicated in CAP, including among pregnant women hospitalized for pneumonia. Most patients with CAP caused by gram-negative bacteria have a predisposing risk factor, such as bronchiectasis, cystic fibrosis, or COPD, and develop severe pneumonia necessitating admission and care in the ICU.
Pregnancy causes a decrease in T-cell function, and pregnant women are at increased risk for severe Listeria infections, including meningitis and sepsis. However, Listeria rarely causes pulmonary infection and would be an unlikely cause of infection in this patient.
Staphylococcus aureus is an increasingly recognized cause of CAP, with risk factors including antecedent viral infection or injection drug use. Maternal S. aureus infection can occur perinatally, related to delivery, surgery, or indwelling lines, but remains a rare cause of CAP in the prenatal period.
- The microbiology of community-acquired pneumonia in pregnancy is similar to that seen in the general population; among patients requiring hospitalization, the most common pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and atypical organisms, including Legionella species, Chlamydia pneumoniae, and Mycoplasma pneumoniae.
Correct answer: C. Normal physiologic change in pregnancy.
Normal physiologic change in pregnancy is the most likely cause of this patient's low serum sodium level. Mild hyponatremia is common in normal pregnancy due to plasma volume increases with water retention (mediated by an increase in antidiuretic hormone levels) greater than sodium retention. An associated drop in serum osmolality of 8 to 10 mOsm/kg H2O and serum sodium concentration of 4 to 5 mEq/L (4 to 5 mmol/L) may occur. As the serum osmolality and sodium concentration decrease, a new set point is maintained, and thirst occurs in response to osmolality (reset osmostat). No treatment is necessary. Other conditions associated with reset osmostat include quadriplegia, tuberculosis, advanced age, psychiatric disorders, and chronic malnutrition.
Primary polydipsia should always be considered in the differential diagnosis of patients with mental illness and hyponatremia, particularly those with schizophrenia who are taking psychotropic drugs. Primary polydipsia presents with hyponatremia, decreased serum osmolality, and decreased urine osmolality, reflecting suppressed antidiuretic hormone (ADH) levels in response to water overload. Primary polydipsia is a rare cause of hyponatremia, and the volume of water intake would need to be very large to induce hyponatremia. This patient is not at risk for primary polydipsia.
Hypovolemia causes stimulation of the sympathetic nervous system, activation of the renin-angiotensin-aldosterone axis, and release of ADH. These adaptive responses allow volume maintenance at the expense of a low serum sodium with excessive water intake. Blood pressure in pregnant women begins to lower in the first trimester and reaches a nadir in the second. Furthermore, she is asymptomatic, and ADH release is therefore not likely to be induced by this level of blood pressure.
The syndrome of inappropriate antidiuretic hormone (SIADH) secretion may be associated with stress and pain; however, hyponatremia does not develop acutely. Although SIADH could have preceded the patient's car accident, she has no risk factors for SIADH (central nervous system disorders, pulmonary disorders, infection, drugs, postoperative status, tumors), and normal pregnancy is a more likely cause of her low serum sodium level.
- Mild hyponatremia is common in normal pregnancy due to plasma volume increases with water retention greater than sodium retention; no treatment is necessary.
Correct answer: E. Ventilation-perfusion lung scan.
A ventilation-perfusion (V/Q) lung scan should be performed next. Pregnant patients with pulmonary embolism (PE) present with symptoms (like dyspnea) that may overlap with symptoms of pregnancy, so a high index of suspicion is needed. New-onset cough is the presenting finding in 24% of pregnant women with PE. Doppler studies may be negative if the primary clot is in the pelvic veins; if results are negative, evaluation for venous thromboembolism requires imaging of the lung. V/Q scanning should be the initial study in pregnant patients. If the V/Q scan is normal, PE can be reliably excluded. If the V/Q scan is strongly positive, showing perfusion defects without matched ventilation abnormalities in this patient with no asthma or underlying lung disease, PE can be reliably diagnosed and therapy initiated.
CT angiography, the gold standard in the diagnosis of PE in most patients, should not be the initial study in pregnant patients because of radiation exposure to both the mother and the fetus. CT angiography should be reserved for instances when the V/Q scan is equivocal.
D-dimer assays are used to guide venous thromboembolism diagnosis in nonpregnant patients with low probability of disease, but D-dimer levels are elevated during pregnancy, with assays only 73% sensitive and 15% specific in this population. Additionally, D-dimer level should be determined only in patients with a low theoretical suspicion for PE. This patient has a moderate or high presumed likelihood.
Magnetic resonance pulmonary angiography has not been evaluated in pregnant patients, but in nonpregnant patients, the sensitivity for PE is only 85% (although the specificity is 98%). In addition, the long-term effects of gadolinium on the fetus are unknown.
Pulmonary function testing would be helpful to rule out bronchospastic disease as a cause for the patient's cough, but it should be done only after the more life-threatening diagnosis of PE is ruled out.
- In the presence of normal Doppler studies of the lower extremities, ventilation-perfusion lung scanning is the initial lung imaging study to evaluate for pulmonary embolism in pregnant patients; D-dimer testing has no diagnostic role.
Correct answer: A. Plasmodium falciparum.
This pregnant woman has contracted Plasmodium falciparum malaria after visiting a part of the world where malaria is endemic. Her clinical presentation and peripheral blood smear showing many parasitized erythrocytes demonstrating signet ring forms, together with the absence of trophozoites and schizonts, are typical for infection with P. falciparum. Of returning travelers with acute and potentially life-threatening febrile diseases, P. falciparum malaria accounts for most infections. Furthermore, pregnant women are at increased risk of severe disease and a heightened mortality rate, which is likely related to a reduced immune response. Additionally, effects on the microvasculature and sequestering of organisms in the placenta during pregnancy are known to significantly increase the risk of miscarriage, premature delivery, low-birth-weight neonates, congenital infection, and fetal demise.
Accurate identification of P. falciparum and Plasmodium knowlesi is critical because of the risk for severe and potentially lethal infection. P. falciparum should be suspected if the patient traveled to Africa, symptoms begin soon after return from an endemic area, and the peripheral blood smear shows a high level of parasitemia. P. knowlesi is a more recently recognized human pathogen; infection may be severe because of high levels of parasitemia. Examination of the peripheral blood smear reveals all stages of the parasite. The epidemiologic history is helpful because P. knowlesi is not encountered in Africa but rather South and Southeast Asia.
Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax are all associated with a low or very low degree of parasitemia, typically less than 2%, and although the risk of recurrence is high, with the exception of P. vivax, the risk for severe disease is low.
- Plasmodium falciparum infection should be suspected if the patient traveled to Africa, symptoms begin soon after return from an endemic area, and the peripheral blood smear shows a high level of parasitemia.
Correct answer: B. Echocardiography.
Echocardiography is the most appropriate diagnostic test to perform next. The patient's symptoms, cardiac examination, and electrocardiography suggest pulmonary hypertension (PH). PH is associated with significant morbidity and a 30% to 50% mortality rate. Prevalence is approximately 10% in nonpregnant patients but increases in women with sickle cell disease (SCD) who become pregnant. Risk factors for development of PH include severity of anemia, iron overload from transfusions, and history of thromboembolic disease. Although cardiac ultrasonography may underestimate the severity of PH, it remains a useful initial noninvasive screening test even if right heart catheterization is eventually required to more definitively evaluate the hemodynamics.
Cardiac MRI would be useful in evaluating infiltrative cardiomyopathy from iron overload or amyloidosis. Secondary iron overload is seen in SCD but invariably in the setting of multiple blood transfusions over years of time, a history that is lacking in this patient.
Although chest pain could be associated with coronary artery disease and angina, patients with SCD are not especially predisposed to this complication. Exercise stress testing would be contraindicated in those with suspected severe PH and a recent episode of exertion-triggered syncope.
Although pregnancy is a risk factor for dissecting thoracic aortic aneurysm, it is somewhat debated whether additional conditions, such as sustained hypertension, Marfan syndrome, or other connective tissue disorders, are required. This patient's clinical features do not warrant aortography before additional tests are performed, including cardiac ultrasonography.
- Pulmonary hypertension, a known complication in sickle cell disease, may worsen during pregnancy and should be initially evaluated by echocardiography.
Correct answer: B. Emergent delivery.
The most appropriate management of this patient is emergency delivery of the fetus. Several disorders are characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia during pregnancy. Pre-eclampsia, HELLP (Hemolysis, Elevated Liver enzymes, and Low Platelets) syndrome, and thrombotic thrombocytopenic purpura–hemolytic uremic syndrome (TTP-HUS) have different clinical features but with significant overlap. Pre-eclampsia typically presents with hypertension, peripheral edema, and proteinuria, most commonly in the third trimester of pregnancy. TTP-HUS is characterized by MAHA and thrombocytopenia developing in the first or second trimester. Additionally, neurologic findings and fever are more common in TTP-HUS than in the other syndromes. HELLP syndrome is characterized by right upper quadrant pain and elevated liver enzyme levels. Disseminated intravascular coagulation parameters may be found in patients with pre-eclampsia and HELLP syndrome but should be absent in those with TTP-HUS. This patient has pre-eclampsia, defined as hypertension (systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg) after the 20th week of gestation with edema and proteinuria, which requires immediate delivery. Symptoms usually resolve with delivery. HELLP syndrome is similarly treated.
Eculizumab is used to treat atypical hemolytic uremic syndrome (HUS), which is the most common form of HUS in pregnancy. It is associated with congenital defects in the alternate pathway of the complement system. Although this patient has proteinuria, the normal creatinine level makes this an unlikely diagnosis because marked kidney disease is a hallmark of this disorder.
High-dose glucocorticoids would be useful to treat immune thrombocytopenic purpura (ITP) in pregnancy, especially toward the end of the third trimester. ITP is diagnosed when an isolated thrombocytopenia is discovered, but it is not associated with hypertension, proteinuria, or schistocytes on the peripheral blood smear.
Although she has thrombocytopenia, fragmented erythrocytes, and headache, her elevated blood pressure, edema, and proteinuria point to pre-eclampsia as a more likely diagnosis than TTP. Therefore, plasma exchange would not be appropriate.
- Pre-eclampsia, HELLP (Hemolysis, Elevated Liver enzymes, and Low Platelets) syndrome, and thrombotic thrombocytopenic purpura–hemolytic uremic syndrome can all present with microangiopathic hemolytic anemia and thrombocytopenia during pregnancy; pre-eclampsia is defined by hypertension, edema, and proteinuria after the 12th week of gestation.