Question: A 25-year-old woman presents for a new patient physical exam. Aside from occasional shin splints, she has a relatively unremarkable medical history. She takes oral contraceptive pills and a multivitamin daily. All of her age appropriate immunizations are up to date. Her periods have been regular, occurring once every 28 to 30 days with normal flow. She is sexually active with 2 partners, who use condoms routinely. Her prior pap smear was performed last year and was normal. Her mother has diabetes and coronary artery disease, and her father passed away at age 45 after being diagnosed with colon cancer at age 40. Her grand-aunt underwent bilateral mastectomies after being diagnosed with breast cancer at age 60. Her temperature is 36.7°C (98°F), blood pressure is 115/80 mmHg, pulse is 65/min, respirations are 12/min, and oxygen saturation is 100% on room air. Her physical exam is within normal limits. Which of the following is the most appropriate recommendation for this patient?

Answer: Colonoscopy in 5 years

Explanation:
This patient is presenting for a health evaluation with a family history significant for her father's death due to colon cancer at age 45. She should thus get a colonoscopy when she reaches the age 10 years prior to her father's age of diagnosis or in 5 years (at age 30).

The age threshold for colon cancer screening varies based on the patient's risk factors, including family history of colon cancer, inflammatory bowel disease, and/or genetic disorders. In the absence of significant risk factors, colonoscopies can be used for screening starting at age 45 and repeated every 10 years if results are normal. If there is family history of colon cancer (one or more first degree relatives, including parent, sibling, or child), colonoscopies should be recommended starting at age 40 or 10 years prior to the age of the family member's diagnosis, whichever is earlier. Polyps or grossly abnormal colon tissue may be biopsied for grading and guide further diagnostic imaging workup.

Aasma et al. review the clinical guidelines for colorectal cancer screening. They found that recent epidemiological data shows an increase in the incidence of colorectal cancer in individuals younger than 50 years. They recommend starting colonoscopy screening at 45 years of age in the average-risk adult population.

Incorrect Answers:
Answer B: Colonoscopy in 10 years is reasonable, but it is not the earlier of the 2 age thresholds mentioned above.

Answer C: Pap smear with HPV DNA screening for cervical cancer is indicated every 5 years for women aged 30 to 65 who wish to extend the screening interval from the 3 year interval for pap smear alone.

Answer D: Pap smear alone is indicated every 3 years for women of ages 21 to 65.

Answer E: Mammogram to screen for breast cancer is recommended every 2 years for women aged 50 to 74.

Bullet Summary:
For patients with a family history of colon cancer, screening should start at age 40 or 10 years prior to the age of the family member's diagnosis, whichever is earlier.


Question: A 23-year-old woman presents to the emergency department for evaluation of fever and chills over the last several days along with a progressive rash and diarrhea. She had nasal septoplasty performed 1 week prior and has had nasal packing in place since that time. Her rash has progressed and the skin on her hands is "peeling." She has no significant medical history and takes no medications. Her temperature is 102°F (38.9°C), blood pressure is 84/54 mmHg, pulse is 160/min, respirations are 22/min, and oxygen saturation is 99% on room air. Exam reveals an ill-appearing woman. A diffuse, macular, erythematous rash is noted with desquamation over the patient's hands as shown in Figure A. Bilateral conjunctivitis is noted. The patient's nasal packing is removed revealing copious, foul-smelling, purulent discharge. Which of the following pathogens is likely responsible for this patient's condition?

Answer: Staphylococcus aureus

Explanation:
This patient with fever, diarrhea, and a diffuse, erythematous rash with prolonged nasal packing in place likely has developed toxic shock syndrome. Toxic shock syndrome occurs most commonly due to infection with Staphylococcus aureus.

Toxic shock syndrome (TSS) occurs due to infection with Staphylococcal or Streptococcal species that produce "super-antigen" toxins, such as TSST-1 produced by S. aureus. These toxins bind directly to the MHC-II receptor on T cells with high affinity causing a massive, sustained cytokine release. The result is a "cytokine storm" causing an intense inflammatory reaction and distributive shock. These infections arise in the setting of a retained tampon or retained nasal packing following nasal surgery; however, this is not always the case. The clinical presentation of TSS is characterized by fever, nausea, vomiting, diarrhea, conjunctivitis, and a diffuse "sunburn-like" rash. Desquamation of the palms and soles typically occurs during recovery, 1-2 weeks after the acute phase of the illness. The initial management of TSS begins with broad spectrum antibiotic therapy. Typical regimens include vancomycin, cefepime, and clindamycin. The initial antibiotic regimen should cover methicillin-resistant Staph aureus. Clindamycin is always included due to its ability to suppress bacterial protein production, therefore limiting the production of bacterial toxins. Once a causative organism is identified, antibiotic therapy may be narrowed, though clindamycin is usually administered for the duration of treatment.

Figure A is the classic generalized and erythematous macular/desquamating rash of toxic shock syndrome.

Incorrect Answers
Answer A: Borrelia burgdorferi is a spirochetal bacteria that causes Lyme disease. A erythematous, bulls-eye shaped rash would be expected.

Answer B: Neisseria meningitidis causes meningococcemia and meningitis. Fever is common, although a purpuric rash and signs of meningeal irritation would be expected. Patients are often profoundly unstable.

Answer C: Rhinovirus is the viral pathogen most commonly responsible for the common cold that causes minor symptoms including a cough, runny nose, fever, and aches.

Answer D: Rickettsia rickettsii causes rocky mountain spotted fever which presents with a high fever, headache, malaise, and a centripetal maculopapular rash that starts on the extremities and migrates to the trunk. It is a tick-borne illness.

Bullet Summary:
Toxic shock syndrome classically develops in patients with prolonged use of nasal packing, and presents with fever, diarrhea, a diffuse erythematous rash, and shock.


Question: A 6-week-old girl presents with her parents to the pediatrician for blood-streaked diapers. The patient is breastfed every 2-3 hours and voids 10-12 times daily. The patient previously had several soft stools per day that ranged in color from mustard yellow to dark green. Over the past 2 days, the patient’s stools have become looser and streaked with blood. The patient has also regurgitated several of her feedings in the last few days. Neither the vomit nor bloody stools have seemed to bother the patient. The patient’s weight continues to trend along the 50th percentile. The patient’s temperature is 98.4°F (36.9°C), blood pressure is 66/51 mmHg, pulse is 127/min, and respirations are 26/min. On physical exam, the patient appears well nourished and is cooing. Her abdomen is soft and non-tender. Physical exam reveals the finding seen in Figure A. Which of the following is the most likely etiology of this patient’s presentation?

Passage of gastric contents into esophagus

Answer: Non-IgE-mediated immunologic reaction

Explanation:
This patient presents with new regurgitation, blood-streaked stools, and eczema, which is consistent with proctocolitis secondary to milk-protein allergy. This type of delayed onset milk-protein allergy is a non-IgE mediated immunologic reaction.

Allergy to cow’s milk is the most common food allergy in children and encompasses both IgE-mediated and non-IgE-mediated reactions. IgE-mediated reactions occur minutes to 2 hours after ingestion of the allergen and range from mild symptoms to anaphylaxis. Milk protein-induced enterocolitis and proctocolitis are non-IgE-mediated reactions that present by 6 months of life with regurgitation or vomiting and bloody stools. Management of milk protein-induced enterocolitis and proctocolitis involves the elimination of cow’s milk and soy from the mother’s diet if the infant is breastfed or switching to a hydrolyzed formula if the infant is formula fed.

Giannetti et al. review the evidence regarding the diagnosis and treatment of milk protein allergy in infants. They discuss how the selective elimination of certain proteins from the diet is usually effective. They recommend considering oral immunotherapy as an adjuvant in the treatment of this disease.

Figure/Illustration A is a clinical photograph demonstrating the physical exam finding of eczema (red circle), which is commonly found in infants with an allergy to milk protein.

Incorrect Answers:
Answer A: Congenital enzyme deficiency describes lactose intolerance, in which there is an absence of lactase activity in the small intestine. Lactose intolerance classically presents with abdominal pain, bloating, flatulence, and diarrhea. Treatment is with diet modification.

Answer C: Hypertrophy of the sphincter muscle describes the pathogenesis of pyloric stenosis, which presents in patients between 3- and 6-weeks of age with non-bilious, projectile vomiting. Treatment is with surgical pyloromyotomy.

Answer D: Passage of gastric contents into the esophagus describes gastroesophageal reflux, which may present with regurgitation or vomiting. Treatment is with positioning but can include proton pump inhibitors in refractory cases.

Answer E: Telescoping of the intestine describes intussusception, which presents with sudden-onset severe, crampy, abdominal pain with non-bilious vomiting and “currant jelly” stools. Intussusception is rare before 3 months of age and presents with intermittent episodes of pain. Initial treatment is with air or contrast enema.

Bullet Summary:
Milk-protein allergy presents in infants between 2- to 8-weeks of age with regurgitation or vomiting, blood-streaked stools, and eczema, and management involves the elimination of cow’s milk and soy from the infant’s diet.


Question: A 3-day-old boy is evaluated in the hospital nursery for the delayed passage of meconium. The patient is breastfed, has been feeding well every 2 hours, and is urinating over 8 times per day. He was born at 35 weeks gestation to a 27-year-old G4P4 mother. The patient is of Ashkenazi Jewish descent and the patient’s parents refused all prenatal genetic testing. The pregnancy was uncomplicated until the patient’s mother had a spontaneous rupture of membranes at 35 weeks of gestation. The patient’s 3 older siblings are all healthy. The patient’s temperature is 98.2°F (36.8°C), blood pressure is 48/32 mmHg, pulse is 164/min, and respirations are 48/min. On physical exam, he appears to be in moderate distress. He has no dysmorphic features, and his abdomen is distended and non-tender. Bowel sounds are absent. Which of the following is the most appropriate next step in management?

Answer: Abdominal radiograph

Explanation:
Delayed passage of meconium should be evaluated with an abdominal radiograph to rule out bowel perforation. Patients with a perforation require emergency surgery.

All neonates should pass meconium in the first 48 hours of life. Patients that fail do to so should be evaluated with an abdominal radiograph to exclude the possibility of bowel perforation. If free air is seen on the abdominal radiograph, patients should be taken for emergent surgery to repair the perforation. If bowel perforation is ruled out, a workup should be done to determine the etiology of the delayed passage, which would most likely include a contrast enema to differentiate between meconium ileus and Hirschsprung disease. Treatment is with meconium removal or excision of the defective segment respectively.

Adams and Stanton review the evidence regarding the diagnosis and treatment of neonatal bowel obstruction. They discuss how malrotation, jejunoileal atresia, duodenal atresia, and colonic atresia are common causes of this finding. They recommend surgical management of these conditions.

Incorrect Answers:
Answer A: An abdominal radiograph would be faster than an abdominal CT to rule out an indication for emergency surgery. The use of CT should also be restricted in the pediatric population due to the radiation exposure involved. Adult patients with unclear radiographic findings can be further assessed using a contrast CT scan.

Answer C: Contrast enema is the test of choice to differentiate meconium ileus from Hirschsprung disease, but the most important first step is to rule out bowel perforation. Patients who do not have perforation can then undergo this test to determine the etiology of failure to pass meconium.

Answer D: Sweat testing would aid in the diagnosis of cystic fibrosis, particularly in this patient who has had no prenatal screening. The first step in management should be an abdominal radiograph to rule out bowel perforation. Cystic fibrosis can be treated with pancreatic enzyme replacement and pulmonary therapy.

Answer E: Upper gastrointestinal series is used to make the diagnosis of intestinal malrotation, which more commonly presents with bilious vomiting secondary to midgut volvulus rather than the delayed passage of meconium. Treatment is with surgical derotation.

Bullet Summary:
Neonates who fail to pass meconium in the first 48 hours of life should be urgently evaluated with an abdominal radiograph to rule out bowel perforation.


Question: A 27-year-old woman presents for her first prenatal visit at an estimated gestational age of 16 weeks and 4 days by last menstrual period. She is presenting late to prenatal care due to significant anxiety about her pregnancy, as she and her husband had struggled with infertility for several years prior to conceiving. She has had nausea and vomiting for about 2 months, tender and swollen breasts, and cravings for foods she typically does not eat. She took a pregnancy test about 10 weeks ago and was too nervous to read the result immediately. After 24 hours, she saw that it was positive. The patient has a past medical history of bulimia nervosa but has not been symptomatic in 2 years. She also had an appendectomy at age 15 for appendicitis. She is a Ph.D. student and her husband is a physician. Her temperature is 98.5°F (36.9°C), pulse is 75/min, blood pressure is 122/76 mmHg, and respirations are 13/min. The patient’s affect is normal and she is pleasant and excited about her pregnancy. A physical exam is notable for abdominal distension but is otherwise unremarkable. Ultrasound is shown in Figure A, and urine human chorionic gonadotropin is negative in the office. Which of the following is the most likely diagnosis?

Answer: Pseudocyesis

Explanation:
This patient presents with signs and symptoms of pregnancy but a nongravid uterus on ultrasound and a negative pregnancy test. The most likely diagnosis is pseudocyesis.

Pseudocyesis, or false pregnancy, most commonly presents with abdominal distension, breast tenderness, nausea, and other typical symptoms of pregnancy. Patients truly believe they are pregnant and may report positive pregnancy tests at home (perhaps due to false positives from waiting too long before reading the result) but office testing is negative. Ultrasound will be normal and show the absence of a developing fetus. The mainstay of treatment is explaining the diagnosis in a therapeutic manner and offering counseling to help patients cope.

Small reviews the evidence regarding the diagnosis and treatment of pseudocyesis. He discusses how this disease is a heterogenous entity involving neuroendocrine changes. He recommends clearly defining the cause of this disease in patients.

Figure/Illustration A shows a transabdominal ultrasound with an empty cavity without signs of pregnancy (red circle). These findings are consistent with pseudocyesis.

Incorrect Answers:
Answer A: Couvade syndrome refers to a “sympathetic pregnancy,” in which a patient experiences pregnancy symptoms when someone close to her is pregnant. This does not apply to this patient because she believes that she is pregnant herself.

Answer B: Delusion of pregnancy is a false and fixed belief about being pregnant, despite factual evidence to suggest otherwise. Patients typically do not experience actual pregnancy symptoms and may have a history of psychotic disorders, both of which are inconsistent with this patient’s presentation. Treatment is with cognitive behavioral therapy.

Answer C: Feigned pregnancy is the intentional falsifying of symptoms for a clear external motive and is a subtype of factitious disorder or malingering. This patient does not express any desire for secondary gain and seems to truly believe that she is pregnant, which is more consistent with pseudocyesis.

Answer E: A recent miscarriage is unlikely, as urine hCG testing often takes up to a month to become negative after pregnancy loss. Furthermore, the patient reports that her symptoms have been consistently present, whereas a miscarriage would typically cause a cessation of pregnancy symptoms.

Bullet Summary:
Pseudocyesis is a somatic symptom disorder in which women believe they are pregnant and experience pregnancy symptoms without an actual pregnancy.


Question: A 26-year-old man presents to the emergency department with fatigue and dark urine over the past day. He was recently diagnosed with cellulitis of his left leg, for which he was prescribed trimethoprim-sulfamethoxazole. He denies having nausea, vomiting, or diarrhea. He has no significant medical history and does not currently take any medications. His temperature is 98.6°F (37°C), blood pressure is 115/72 mmHg, pulse is 98/min, and respirations are 14/min. Physical exam reveals conjunctival icterus, bilateral flank tenderness, and erythema of the left leg. Laboratory workup is performed, and the results are shown below: Serum: Hemoglobin: 7.2 g/dL Total bilirubin: 2.1 mg/dL Direct bilirubin: 0.8 mg/dL Lactate dehydrogenase: 470 U/L Glucose-6-phosphate dehydrogenase: 7 U/gHb (normal: 6-20 U/gHb) Which of the following would most likely be seen on a peripheral blood smear in this patient?

Answer: Degmacytes

Explanation:
This patient presents with hemolytic anemia (low hemoglobin, elevated indirect bilirubin, and elevated lactate dehydrogenase) shortly after starting a sulfa medication (trimethoprim-sulfamethoxazole) in the setting of likely glucose-6-phosphate dehydrogenase deficiency. Degmacytes ("bite cells") will be seen on peripheral blood smears in these patients.

Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency will experience hemolytic anemia when exposed to an oxidizing substance such as sulfa drugs or fava beans. Laboratory tests will show a decrease in hemoglobin and hematocrit levels. Since hemolysis releases intracellular enzymes into the bloodstream, serum levels of lactate dehydrogenase will be increased. Hemoglobin is then metabolized in the spleen into unconjugated bilirubin, which will cause an elevated bilirubin level that is primarily indirect. In the acute setting, G6PD levels will be normal because the most compromised cells have all been hemolyzed. Obtaining a G6PD level in between episodes of hemolysis is therefore required to observe the chronically decreased G6PD in these patients. A peripheral blood smear will reveal degmacytes ("bite cells") and Heinz bodies. Avoidance of oxidative stress to red blood cells is the most important component of management in these patients.

Belfield and Tichy discuss the classic presentation of G6PD deficiency in patients. The authors review oxidizing medications such as rasburicase, primaquine, dapsone, pegloticase, and methylene blue. The authors recommend avoiding initiation of these medications whenever possible until a G6PD diagnostic test has been performed.

Incorrect Answers:
Answer A: Acanthocytes can be seen in patients with liver disease due to defective production of lipoproteins; however, these cells do not undergo acute hemolytic destruction. Patients with abetalipoproteinemia usually present with symptoms consistent with fat-soluble vitamin deficiency such as bleeding (vitamin K) or osteoporosis (vitamin D).

Answer B: Codocytes are most commonly seen in patients with thalassemia but can also generally be seen in all microcytic anemias. Patients with thalassemia will present with chronic anemia without acute episodes of hemolysis. The increased lactate dehydrogenase and bilirubin levels in this patient indicate an acute hemolytic event.

Answer D: Schistocytes can be seen in thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC). Patients with TTP present with thrombocytopenia, microangiopathic hemolytic anemia, fever, neurologic symptoms, and acute kidney injury. DIC is a common downstream pathway for many processes such as sepsis, malignancy, and eclampsia; however, it would present with diffuse clotting and bleeding from all sites.

Answer E: Spherocytes can be seen in hereditary spherocytosis, which may result in hemolysis during times of acute stress; however, this patient denies symptoms of nausea, vomiting, or diarrhea. Instead, the hemolysis in response to new foods is most likely due to exposure to oxidizing substances such as trimethoprim-sulfamethoxazole.

Bullet Summary:
Patients with glucose-6-phosphate dehydrogenase deficiency will experience hemolytic anemia in response to oxidizing substances and will have degmacytes (bite cells) on peripheral blood smear.


Question: A 68-year-old man presents to the emergency department with right ear pain that he developed 4 days prior, and it has progressively worsened. The pain is worse at night. He has associated fever and chills. This morning, he awoke with purulent, foul-smelling discharge on his pillow. He has a history of type II diabetes mellitus and hypertension. He takes metformin, insulin, and lisinopril. His temperature is 102.2°F (39.0°C), blood pressure is 130/87 mmHg, pulse is 110/min, and respirations are 16/min. The patient is toxic in appearance and in mild distress due to pain. Examination of the external ear reveals findings shown in Figure A. Granulation tissue and purulent drainage are noted in the external auditory canal. Physical exam is otherwise unremarkable. Which of the following is the most appropriate therapy for this patient?

Answer: Vancomycin and piperacillin-tazobactam

Explanation:
The patient in this vignette most likely has malignant otitis externa (also referred to as necrotizing otitis externa), which is a life-threatening infection requiring therapy with intravenous anti-pseudomonal and broad-spectrum antibiotics. Piperacillin-tazobactam and vancomycin is an appropriate initial regimen.

Malignant otitis externa is an invasive infection of the external auditory canal and skull base, and is seen almost exclusively in immunocompromised patients. Patients with poorly controlled type II diabetes mellitus are at particularly increased risk. The infection spreads from the floor of the ear canal to the nearby tissues including the bones at the base of the skull and the temporomandibular joint. The resulting skull base osteomyelitis distinguishes the "necrotizing" or "malignant" presentation of otitis externa. Patients often present with severe otalgia and purulent drainage from the external auditory canal. Granulation tissue in the external auditory canal is a characteristic exam finding. Pseudomonas aeruginosa is the causative organism in most cases of necrotizing otitis externa. Therefore, intravenous antibiotics with sufficient coverage of Pseudomonas are the therapy of choice. As infection progresses, involvement of cranial nerves with resultant palsy may be observed.

Aaraj et. al review the clinical manifestations, diagnosis and management of malignant otitis externa. They note the risk for this disease among patients with diabetes or other etiologies of an immunocompromised state. They recommend management with intravenous ciprofloxacin.

Figure A shows the external ear of a patient with malignant otitis externa. Note the classic granulation tissue at the cartilage-bone junction and crusted, purulent discharge.

Incorrect Answers:
Answer A: Intravenous acyclovir would be appropriate for suspected herpes zoster, which may present with ear pain and a vesicular rash in the external auditory canal. This patient's granulation tissue in the external auditory canal and purulent drainage make malignant otitis externa more likely.

Answer B: Oral amoxicillin may be appropriate for management of acute otitis media which presents with ear pain and a distended tympanic membrane that is immobile.

Answer C: Ceftriaxone is appropriate coverage for cellulitis which presents with warmth, erythema, and tenderness of the skin. It would be too narrow of spectrum to treat malignant otitis externa.

Answer E: Topical ofloxacin may be appropriate for some cases of simple otitis externa ("swimmer's ear") which presents with ear pain and drainage in young, healthy patients who swim regularly. Patients are well-appearing.

Bullet Summary:
Malignant otitis externa is an invasive infection of the external auditory canal and skull base that requires management with broad-spectrum intravenous antibiotics that cover Pseudomonas aeruginosa.


Question: An 8-week-old boy presents with his mother to the pediatrician for a well visit. The patient has been breastfed since birth, and usually feeds for 30 minutes every 2-3 hours. The patient’s mother is concerned that her milk production is not keeping up with the patient’s nutritional requirements. She reports that about 2 weeks ago the patient began regurgitating breastmilk through his nose and mouth after some feeds. He seems mildly upset during the episodes of regurgitation but usually settles down quickly and is hungry again soon afterwards. His mother has already tried limiting the volume of each feed, which seems to have reduced the frequency of regurgitation. She denies any diarrhea, hematochezia, or family history of food allergies. Her older son had a similar problem with vomiting that resolved around 12 months of age. Four weeks ago, the patient’s height and weight were in the 40th and 34th percentiles, respectively. His height and weight are now respectively in the 37th and 36th percentiles. His temperature is 98.6°F (37°C), blood pressure is 72/49 mmHg, pulse is 121/min, and respirations are 32/min. On physical exam, the patient is cooing in his mother’s lap and smiles reciprocally with her. He lifts his head and shoulders off the examination table when placed in the supine position. His abdomen is soft, non-tender and non-distended. Bowel sounds are normoactive. Which of the following is the most appropriate next step in management?

Reassurance and counseling on positioning

Answer: Reassurance and counseling on positioning

Explanation:
This patient presents with regurgitation after feeding, appropriate appetite after episodes of regurgitation, and good weight gain, which suggests a diagnosis of uncomplicated gastroesophageal reflux. The most appropriate next step in management is reassurance and counseling on proper positioning.

Physiologic or uncomplicated gastroesophageal reflux usually presents in patients in the first few months of life with frequent regurgitation or vomiting, sustained appetite after regurgitation, and minimal irritability. The most appropriate first step in management is reassurance and counseling parents to position patients upright for 20-30 minutes after feeding. For patients with persistent symptoms, parents should be encouraged to provide lower volume feeds more frequently throughout the day, and consider a milk-free diet to address possible underlying cow’s milk allergy. Treatment with a proton pump inhibitor is reserved for intractable cases. For most patients, gastroesophageal reflux self-resolves by 1 year of age.

Chabra and Peeples review the evidence regarding the treatment of neonatal GERD. They discuss how alterations in the infant's environment and feeding pattern are effective in most cases. They recommend proton pump inhibitors if conservative treatments are not effective.

Incorrect Answers:
Answer A: Initiating a proton pump inhibitor is appropriate for infants with gastroesophageal reflux disease who have failed management with lifestyle changes. This patient has uncomplicated gastroesophageal reflux without any signs of feeding refusal, worsening irritability, or nutritional compromise.

Answer B: Obtaining an abdominal ultrasound would evaluate for pyloric stenosis, which presents with non-bilious, projectile vomiting rather than the regurgitation that this patient’s mother is describing. An abdominal ultrasound would be the appropriate next step in management for patients who present with a description of more forceful vomiting or have a classic “olive-shaped” mass in the epigastrium on physical exam.

Answer D: Recommending modification of the mother’s diet would be appropriate if this patient had more severe symptoms that were refractory to lifestyle changes. It would also be appropriate if the patient had signs of an underlying allergy to cow’s milk or soy protein, such as blood-streaked stools.

Answer E: Switching to a hydrolyzed formula would be appropriate for formula-fed patients with refractory symptoms of gastroesophageal reflux disease or signs of an allergy to cow’s milk or soy protein. Unless the patient has evidence of severe nutritional compromise, continued breastfeeding should be encouraged for breastfed patients with possible modification of the mother’s diet to eliminate cow’s milk or soy if an allergy is suspected.

Bullet Summary:
Uncomplicated gastroesophageal reflux in infants should be treated with reassurance and counseling to position the infant upright for 20-30 minutes after feeding.


Question: A 65-year-old man presents to the emergency department for evaluation of left arm and leg weakness. He was walking in the park about 45 minutes prior to arrival when the patient stumbled and fell. He had sudden weakness in his left leg and was unable to grasp a handrail with his left hand. He currently takes no medications. His temperature is 98.0°F (36.6°C), blood pressure is 128/89 mmHg, pulse is 130/min, and respirations are 18/min. On exam, he has 3/5 strength in the left upper and lower extremities and a left-sided facial droop. A non-contrast CT scan of the head is performed, which suggests parenchymal ischemia in the distribution of the right middle cerebral artery. An ECG is performed, as shown in Figure A. He is given intravenous alteplase with rapid improvement in his strength deficits and facial asymmetry. Which of the following is the most appropriate long-term therapy for secondary stroke prevention for this patient?

Answer: Rivaroxaban

Explanation:
This patient presents with acute onset unilateral left-sided weakness secondary to an ischemic stroke in the right MCA in the setting of an irregularly irregular rhythm without P waves (suggesting that he had an embolic stroke secondary to atrial fibrillation). First-line primary and secondary stroke prevention in patients with atrial fibrillation involves long term anticoagulation with a direct oral anticoagulant (DOAC) such as rivaroxaban.

Atrial fibrillation is caused by uncoordinated atrial contractions, typically due to atrial enlargement, inflammation, or infiltrative disease. Atrial fibrillation can lead to the formation of a thrombus, typically in the left atrial appendage, which can embolize to the brain and lead to an ischemic stroke. For this reason, there is a low threshold to start patients on long term anticoagulation for both primary and secondary stroke prevention (risk stratification is done with the CHA2DS2-VASc score, which considers several cardiovascular risk factors, age, sex, and diabetes). First-line long term anticoagulation is a DOAC medication such as apixaban, dabigatran, rivaroxaban, or edoxaban. Delayed initiation of anticoagulation is recommended at 4-14 days after a stroke, due to the interim risk of hemorrhagic conversion. Further management of atrial fibrillation includes a rate control agent such as a beta blocker or a calcium channel blocker.

JS Alpert reviews the latest American Heart Association/American College of Cardiology guidelines regarding atrial fibrillation. The article reports that for stroke prevention in atrial fibrillation, DOACs are first-line compared to warfarin due to a decreased risk for bleeding with DOACs. In patients with moderate to severe mitral stenosis or a mechanical heart valve, warfarin is the preferred agent.

Figure/Illustration A shows an ECG with an irregularly irregular rhythm (highlighted by the spacing of blue arrows) and no discernable P waves before QRS complexes, which is characteristic of atrial fibrillation.

Incorrect Answers:
Answer A: Aspirin exerts antiplatelet adhesion effects through the inhibition of cyclooxygenase. Patients with atrial fibrillation who are at low risk for stroke (CHA2DS2-VASc score of < 1) can use aspirin monotherapy for stroke prophylaxis. This patient presented after a stroke and will require long term anticoagulation, not anti-platelet monotherapy for stroke prevention.

Answer B: Atorvastatin is an HMG-CoA reductase inhibitor, which works to lower LDL cholesterol and triglycerides, and increase HDL cholesterol. It is most useful in secondary stroke prevention in patients who have suffered a thrombotic or thromboembolic stroke secondary to atherosclerosis. This patient may have atherosclerosis and could benefit from statin therapy; however, anticoagulation for his underlying atrial fibrillation is the highest priority.

Answer C: A cardiac pacemaker is indicated in a large variety of cardiac conditions that primarily involve sinus node dysfunction or high-grade atrioventricular block. Atrial fibrillation does not typically require a pacemaker, as it is typically managed with rate control agents such as beta-blockers, calcium channel blockers, digoxin, or with electrical cardioversion. Rate control will not lower the stroke risk, and thus long-term anticoagulation is required.

Answer E: Warfarin has historically been a mainstay anticoagulant for stroke prevention in atrial fibrillation. DOACs are non-inferior to warfarin, and have a lower risk of bleeding. Note, only the initiation of warfarin requires a heparin bridge to mitigate the transient protein C deficiency that results in a temporary hypercoagulable state (often presenting as warfarin skin necrosis).

Bullet Summary:
For patients who present with an ischemic stroke secondary to a cardiac embolus from atrial fibrillation, first-line long term anticoagulation is a direct oral anticoagulant (apixaban, dabigatran, rivaroxaban, or edoxaban).


Question: A girl presents to her pediatrician for a well-child visit. Her mother reports that she is eating well at home and sleeping well throughout the night. She can jump and walk up and down stairs with both feet on each step. In the doctor’s office, the patient builds a 6-cube tower and imitates a circle. She seems to have a vocabulary of over 50 words that she uses in 2-word sentences. The patient enjoys playing near other children and sometimes argues over toys with her older brother. Her temperature is 98.6°F (37°C), blood pressure is 92/56 mmHg, pulse is 106/min, and respirations are 23/min. On physical exam, she appears well developed and well nourished, and she is following along her growth curves. The child is assessed as developmentally normal. Which of the following is an additional milestone associated with this child’s age?

Answer: Follows two-step commands

Explanation:
This patient is able to walk up and down stairs, can build a 6 cube tower, has a 50+ word vocabulary, and uses 2-word phrases, which suggests she is 2 years of age. Another milestone at 2 years of age is following 2-step commands.

In the gross motor category, a child at 2 years of age should be able to jump and walk up and down stairs with both feet on each step. In the fine motor category, the child should be able to copy a line or circle and build a tower of 6 cubes. In the language category, the child should be using over 50 words and putting them together in 2-word phrases. In the social category, a child should be participating in parallel play. In the receptive language category, a child should be able to follow a 2-step command. Persistent developmental delays should prompt investigation for correctable causes such as hearing loss.

Scharf et al. review the evidence regarding the use of developmental milestones in assessing children. They discuss how early identification of delays can allow for referral to required services. They recommend paying special attention to sensory function to avoid missing a correctable hearing deficit.

Incorrect Answers:
Answer A: Balancing on 1 foot is a milestone at 3 years of age. A 2-year-old child would not be expected to maintain balance in that position.

Answer B: Cutting with scissors is a milestone at 3 years and 6 months of age. A 2-year-old child would not be expected to be able to hold or use scissors correctly.

Answer D: Pointing to one body part is a milestone at 15 months of age. A 2-year-old child should be able to point to 5-6 body parts.

Answer E: Turning pages in a book is a milestone at 16 months of age. It would not be considered a milestone for a 2-year-old child.

Bullet Summary:
At 2 years of age, a child should be able to walk up and down stairs, build a tower of 6 cubes, use a vocabulary of over 50 words in 2-word phrases, and follow a 2-step command.


Question: A 45-year-old morbidly obese woman with a history of asthma and type 2 diabetes mellitus presents to her primary care physician for advice on weight loss. She thinks that her husband is having sex with other women because they have not had sex over the past year. She feels that her co-workers also disrespect her for her weight and constant sweat stains around her armpits and chest. She has noticed that the sweat stains get itchy and induce a burning sensation unless she showers or changes her shirt. She has been compliant with her medications, which include albuterol, metformin, glyburide, and atorvastatin. Her temperature is 98.6°F (37°C), blood pressure is 128/85 mmHg, pulse is 91/min, and respirations are 11/min. On physical exam, the patient has a flat affect, with moist oral mucosa and nasal polyps. She denies sinus tenderness. Her neck is thick with a posterior cervical fat pad. During cardiac auscultation, the finding in Figure A is noted below her breasts. What is the most appropriate next step in management for this finding?

Answer: Topical nystatin

Explanation:
This patient has a rash consistent with candidal intertrigo given the location and history of a damp, pruritic rash. The most appropriate next step in management is topical nystatin powder.

Intertrigo is caused by the Candida species and is characterized by pruritic, painful, and erythematous superficial patches surrounded by satellite lesions. They are commonly seen in intertriginous areas such as the breasts, groin, axilla, or abdominal pannus. Obesity and diabetes are significant risk factors. Initial management involves maintaining skin dryness along with medical treatment using topical nystatin, clotrimazole, or miconazole. Persistent lesions may require oral antifungal treatment.

Nobles and Miller review the evidence regarding the diagnosis and treatment of intertrigo. They discuss how these lesions often become infected with Candida. They recommend the use of antifungal medications.

Figure/Illustration A shows candidal intertrigo in the breast fold. Note the satellite lesions that surround the erythematous patch.

Incorrect Answers:
Answer A: Fluconazole is indicated for moderate to severe disease or if the rash is refractory to topical antifungals. Topical antifungal agents should be used before progressing to oral medications.

Answer B: Prednisone is not indicated and would potentially worsen the rash through immunosuppression and exacerbation of the patient's diabetes mellitus.

Answer C: Topical clobetasol is a high-potency corticosteroid. This would not be used because it can promote infection and lead to skin atrophy. Low-potency corticosteroids such as triamcinolone or hydrocortisone can be used as adjuncts for symptom control only.

Answer D: Topical imiquimod is indicated for autoimmune skin diseases such as alopecia areata not for candidal intertrigo. This disease would present with segmental regions of hair loss

Bullet Summary:
The treatment of candidal intertrigo involves topical antifungals including nystatin, clotrimazole, and miconazole.


Question: A 55-year-old woman presents to a primary care physician with persistent nausea and abdominal discomfort. She has experienced these symptoms daily for the past 3 months. She feels bloated and has episodic loose and watery stools. She has a history of hypertension and hyperlipidemia for which she takes amlodipine and atorvastatin. She immigrated from Vietnam 6 months ago. Her temperature is 98.6°F (37.0°C), blood pressure is 110/60 mmHg, pulse is 70/min, and respirations are 18/min. Physical exam reveals a thin-appearing woman in no acute distress. Her mucous membranes are moist. Cardiac and lung examinations are unremarkable. Laboratory results are as follows: Leukocyte count: 13,000/mm^3 Segmented neutrophils: 54% Bands: 2% Eosinophils: 6% Basophils: 0.4% Lymphocytes: 30% Monocytes: 5% A vitamin D level is 26 ng/mL (reference: >= 30 ng/mL). Which of the following is the most appropriate test in making the diagnosis?

Answer: Stool ova and parasite assay

Explanation:
This patient who presents with persistent abdominal discomfort, nausea, bloating, diarrhea, eosinophilia, and signs of malabsorption (thin-appearing, vitamin D deficiency) in the setting of immigration from a resource-limited country most likely has a gastrointestinal parasite infection (Ascaris lumbricoides). The most appropriate next step in management is to obtain a stool ova and parasite assay.

Ascaris lumbricoides is a roundworm that is transmitted via the fecal-oral route (egg ingestion). While most patients are asymptomatic, there can be pulmonary and intestinal manifestations in the early and late phases, respectively. Pulmonary signs include dry cough, dyspnea, fever, and wheezing. Intestinal signs include abdominal discomfort, diarrhea, nausea, vomiting, malabsorption, and/or anorexia. The diagnosis should be suspected in patients with vague abdominal symptoms with travel history to an endemic area. The diagnosis is secured with stool microscopy for eggs or worms. Complications of this condition include intestinal obstruction or hepatobiliary/pancreatic involvement, presenting as biliary colic, obstructive jaundice, and/or ascending cholangitis. Treatment in patients with uncomplicated infection is with anti-helminth therapy (albendazole or mebendazole).

Parija et al. review the epidemiology of helminth infections globally. The authors note that many cases are caused by Ascaris species. They recommend prompt identification of these infections as they can cause lack of school attendance, anemia, and cognitive deficits if left untreated.

Incorrect Answers:
Answer A: Bowel wall biopsy is used in the diagnostic work-up of suspected Whipple disease, which presents with chronic diarrhea, malabsorption, weight loss, and joint symptoms (arthralgias). This disease is progressive over years and would be less likely in this patient with disease onset of 3 months.

Answer B: CT scan of the abdomen is used in the diagnostic work-up of small bowel obstruction, which presents as crampy abdominal pain, constipation, obstipation, and/or vomiting. Bowel obstruction is an acute process that would be unlikely in this patient with chronic symptoms. Although bowel obstruction is a complication of Ascaris infection, this patient has no signs of obstruction. Diarrhea may occur secondary to infection of the colon as well including colitis or diverticulitis; however, these conditions typically cause pain and low grade fever.

Answer C: Lower endoscopy (colonoscopy) is used in the diagnosis of inflammatory bowel disease, consisting of Crohn disease and ulcerative colitis. Ulcerative colitis presents with bloody diarrhea, abdominal pain, weight loss, and fatigue. Eosinophilia would be unexpected, and this patient does not have bloody diarrhea.

Answer E: Stool toxin assay is used to diagnose Clostridioides difficile infection. This presents after recent antibiotic use with watery diarrhea, dehydration, fever, and nausea. It presents acutely and generally without eosinophilia.

Bullet Summary:
Parasitic gastrointestinal infections present with chronic diarrhea, abdominal discomfort, malabsorption, and eosinophilia, and are diagnosed using stool ova and parasite assays.


Question: A 54-year-old man presents to the clinic with 4 weeks of persistently worsening back pain. The pain is localized to 1 spot in his lower back and is worse with physical activity. His medical history is pertinent for intravenous drug use. He has no past surgical history. His temperature is 36.8°C (98.2°F), blood pressure is 118/90 mmHg, pulse is 92/min, respirations are 13/min, and oxygen saturation is 99% on room air. On physical exam, he has midline back tenderness to palpation at L2-L3. Laboratory workup reveals an erythrocyte sedimentation rate of 112 mm/h and C-reactive protein of 10 mg/dL. Which of the following is the most likely diagnosis?

Answer: Osteomyelitis

Explanation:
This patient with a history of intravenous drug use who presents with worsening focal back pain and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) most likely has vertebral osteomyelitis.

Vertebral osteomyelitis typically occurs via three routes: hematogenous spread from a distant site (the most common mechanism), direct inoculation from spinal surgery or trauma, or contiguous spread from adjacent soft tissue infection. Patients usually present with back or neck pain, with or without fever, and the most common clinical finding is local tenderness to percussion over the involved posterior spinous process. Risk factors include injection drug use, degenerative spine disease, prior spinal surgery, infective endocarditis, diabetes mellitus, corticosteroid therapy, and other immunocompromised states. Vital signs may be normal, and laboratory evaluation commonly reveals an elevated white blood cell count, ESR, and CRP. An MRI of the spine is the most appropriate diagnostic test. In stable patients, antimicrobial therapy should be withheld until a microbiological diagnosis is confirmed; once the diagnosis is confirmed, pathogen-directed therapy should then be administered.

Beronius et al. conducted a retrospective study on vertebral osteomyelitis in pursuit of diagnostic criteria to simplify the diagnosis and classification of vertebral osteomyelitis. The authors found that elevated ESR and CRP are found in most patients with vertebral osteomyelitis. The authors recommend clinicians have a high index of suspicion for vertebral osteomyelitis in order to avoid delayed diagnosis.

Incorrect Answers:
Answer A: Ankylosing spondylitis is an inflammatory arthritis of the spine and is often associated with one or more articular or periarticular extraspinal features, including synovitis, dactylitis, and enthesitis. Patients typically present with chronic back pain and loss of mobility before the age of 45.

Answer B: Degenerative spine disease involves osteoarthritis of the spine and is associated with increasing age, presenting commonly as sharp or chronic pain in the neck or back. It typically does not result in radiculopathy, defined as irritation or injury of a nerve root, causing pain, weakness, numbness, or tingling in specific distributions depending on the location of the affected nerve root. Though it is certainly on the differential for this patient, his elevated ESR and CRP make osteomyelitis a more likely diagnosis.

Answer C: Herniated disc can cause a variety of symptoms depending on the position and size of the herniation. If the herniated disk impinges on a nerve, patients may have radiculopathy.

Answer D: Metastatic tumor is typically suspected in patients with back pain in the setting of a known malignancy. The most common primary cancers that metastasize to bone include breast, prostate, thyroid, lung, and renal cancer.

Bullet Summary:
Vertebral osteomyelitis typically presents as focal back pain, with or without fever, with an elevated erythrocyte sedimentation rate and C-reactive protein.


Question: A 46-year-old woman presents to her primary care doctor to request a referral to ophthalmology. Her vision has been steadily declining over the past 2 years and she thinks she needs a prescription for glasses. She further complains that her lips and feet feel numb. Her medical history is notable for medullary thyroid cancer status post total thyroidectomy. Her periods are regular. She enjoys a diverse diet and takes levothyroxine. Her blood pressure is 110/70 mmHg, pulse is 80/min, and respirations are 12/min. She is alert and oriented. Her pupils are equal, round, and reactive to light, but appear opacified. Extraocular movements are intact, albeit slow. Her visual acuity is decreased bilaterally. The remainder of her physical exam is unremarkable. Her basic metabolic panel is shown below: Na+: 139 mEq/L Cl-: 100 mEq/L K+: 4.9 mEq/L HCO3-: 25 mEq/L BUN: 10 mg/dL Glucose: 110 mg/dL Creatinine: 0.8 mg/dL Thyroid-stimulating hormone: 1.5 µU/mL Ca2+: 7.0 mEq/L Phosphorus: 6.5 mEq/L Albumin: 3.6 mg/dL The patient's ECG is shown in Figure A. What is the most likely cause of this presentation?

Answer: Iatrogenic hypoparathyroidism

Explanation:
This patient who presents with cataracts and a prolonged QTc interval on ECG most likely has symptomatic hypocalcemia secondary to the surgical removal of all of her parathyroid glands (iatrogenic hypoparathyroidism).

Thyroid surgery may mandate the removal of parathyroid glands if there is evidence of malignant invasion. One parathyroid gland is enough to maintain eucalcemia, but accidental/intentional removal of all the glands is possible. Less common causes are autoimmune parathyroid destruction or parathyroid infiltration by disorders like sarcoidosis or Wilson disease. Many patients are asymptomatic, but chronic hypocalcemia is associated with increased phosphate levels, prolonged QT interval, Parkinsonian signs, cataracts, and cognitive impairment. Severe, acute hypocalcemia can present with tetany, papilledema, and seizures. Treatment is with calcium and parathyroid hormone replacement.

Clarke et al. review the evidence regarding the diagnosis and etiologies of hypoparathyroidism. They discuss how the most common cause is post-surgical. They recommend obtaining genetic testing in cases where the etiology is unclear.

Figure/Illustration A shows an ECG with a prolonged QTc interval at approximately 500 msec (blue circle).

Incorrect Answers:
Answer A: This patient is mildly hyperkalemic, but her symptoms and signs are not associated with hyperkalemia. Patients with hyperkalemia present with heart palpitations, shortness of breath, chest pain, nausea, or vomiting. ECG will demonstrate peaked T waves.

Answer C: The patient is on levothyroxine with appropriate TSH levels. Hypothyroidism is not associated with QT prolongation. Patients with hypothyroidism will present with cold intolerance, delayed responsiveness, and myxedema coma. Treatment is with increasing the levothyroxine dose.

Answer D: Multiple endocrine neoplasia is associated with medullary thyroid cancer, but this patient has no evidence of additional organ disease. Other signs of multiple endocrine neoplasia include pancreatic tumors, pheochromocytoma, or a Marfanoid habitus. Treatment is with surgical excision of tumors.

Answer E: This patient most likely has a biological reason for her symptoms, so somatization is less likely. Patients with somatizing disorders have psychological distress that manifests as physical symptoms. These patients will not have organic correlates of disease such as abnormal ECG results.

Bullet Summary:
Iatrogenic hyperparathyroidism after the removal of the thyroid gland is the most common cause of hypocalcemia.


Question: A 36-year-old G3P2002 woman presents to her obstetrician’s office for her 1st prenatal visit at 10 weeks and 2 days gestation. She has felt nauseous the last several mornings and has been tired for a few weeks. The patient has had 2 uncomplicated spontaneous vaginal deliveries at full term with her last child born 6 years ago. She is concerned about the risk of Down syndrome in this fetus, as her sister gave birth to an affected child at age 43. She has a history of generalized anxiety disorder, atopic dermatitis, and she is currently on escitalopram. Her temperature is 98.6°F (37.0°C), pulse is 70/min, blood pressure is 121/67 mmHg, and respirations are 13/min. The patient appears anxious, but overall comfortable, and cardiopulmonary and abdominal exams are unremarkable. Pelvic exam reveals normal external genitalia, a closed and soft cervix, a 10-week-sized uterus, and no adnexal masses. Which of the following is the most appropriate next step for definitively determining whether this patient’s fetus has Down syndrome?

Answer: Chorionic villus sampling

Explanation:
This patient is over 35 years of age and concerned about the risk of Down syndrome (trisomy 21) in her fetus at just over 10 weeks gestation. At this gestational age, the most definitive method for determining whether such an aneuploidy is present is chorionic villus sampling (CVS).

CVS, or sampling of the placental tissue, can be performed as early as 10 weeks gestation. This is in contrast to amniocentesis, which should be avoided prior to 14 weeks. There are other screening tests for a patient concerned about aneuploidy; however, only CVS and amniocentesis offer definitive diagnoses. Complications of this procedure include pregnancy loss (at a rate of 1-2%), transverse limb abnormality, rupture of membranes, and chorioamnionitis. Patients should also have counseling if genetic abnormalities are detected using this procedure.

Farina reviews the evidence regarding the complications associated with CVS. He discusses how this procedure is becoming more common as the definitive method of providing an early diagnosis. He recommends being aware of complications such as possible pregnancy loss.

Incorrect Answers:
Answer A: Amniocentesis is a useful tool for the definitive diagnosis of aneuploidy and other genetic conditions. Due to the higher rate of fetal loss at younger gestational ages, it is reserved for those above 14 weeks.

Answer B: The anatomy ultrasound can be helpful in identifying morphologic features that are concerning for Down syndrome, such as a flat nasal bridge or an echogenic cardiac focus. This screening tool is most accurate after 18 weeks gestation.

Answer D: Genetic testing of the patient’s sister may be able to help identify if there is a parental translocation or aneuploidy that led to the child’s Down syndrome. This is much less likely than meiotic nondisjunction due to advanced maternal age, and this would not help diagnose Down syndrome in the patient’s fetus.

Answer E: The nuchal translucency test examines the thickness of the nuchal fold. When the thickness exceeds normal measurements, there is an increased risk of aneuploidy such as Down syndrome, but this is a screening result that would not provide a definitive diagnosis.

Bullet Summary:
Chorionic villus sampling is a definitive method of identifying aneuploidy in fetuses starting at 10 weeks of gestational age.


Question: A 53-year-old man presents to the clinic with a non-tender mass in his right anterior neck. The mass has been slowly enlarging over the past 1 year. He reports no dysphagia, difficulty breathing, or changes to his voice. He also denies heat intolerance, palpitations, tremors, or diarrhea. He has hypertension and hyperlipidemia, for which he takes lisinopril and atorvastatin. He has never smoked cigarettes. His temperature is 37.1°C (98.8°F), blood pressure is 130/84 mmHg, pulse is 86/min, respirations are 12/min, and oxygen saturation is 99% on room air. Bedside ultrasound reveals a 1x2 cm hypoechogenic nodule with microcalcifications in the right thyroid lobe, which is biopsied. Pathology results are shown in Figure A. Which of the following is the most appropriate next step in management?

Thyroidectomy followed by radioactive iodine

Answer: Thyroidectomy followed by radioactive iodine

Explanation:
This patient who presents with a slowly enlarging neck mass has ultrasound (hypoechogenic nodule with microcalcifications) and histology findings (concentrically laminated calcifications called psammoma bodies) consistent with papillary thyroid carcinoma. The most appropriate next step in management would be thyroidectomy followed by radioiodine ablation.

Papillary thyroid carcinoma represents the majority of malignant thyroid cancers. They are slow-growing and are found in the hormone-producing follicular cells of the thyroid. Typically, these tumors are found incidentally on imaging. Risk factors for thyroid malignancy include a history of radiation exposure, female sex, and positive family history. Nodules with minimal uptake on radioactive iodine scan, firm and immobile solitary nodules, and rapidly growing nodules with associated hoarseness are more suggestive of thyroid malignancy. Findings on histology include empty-appearing nuclei with central clearing, psammoma bodies, and nuclear grooves. The treatment is thyroidectomy followed by radioactive iodine ablation of any remaining thyroid cells. Long-term care should include levothyroxine at a dose sufficient to suppress thyroid-stimulating hormone (TSH) release that may stimulate any remaining malignant cells.

Oakley et al. studied if relatives of patients diagnosed as having papillary thyroid carcinoma are at increased risk using a retrospective cohort study. The authors found first-degree relatives were at a 5-fold increased risk, and second-degree relatives were at a 2-fold increased risk. The authors recommend more research into optimal approaches to screening for thyroid cancers.

Figure/Illustration A is a histology section showing a psammoma body (blue circle), which are round, concentrically laminated calcifications that are formed after necrosis of papillary structures. Psammoma bodies and nuclei with central clearing (yellow circle) and nuclear grooves are common histology findings for papillary thyroid carcinoma.

Incorrect Answers:
Answer A: Levothyroxine would be the treatment of choice in hypothyroidism and is important in the long-term care of papillary thyroid carcinoma to suppress the TSH release that may stimulate any remaining malignant cells after treatment (thyroidectomy and radioactive iodine).

Answer B: Methimazole is an agent that blocks thyroid peroxidase, thus inhibiting the synthesis of thyroid hormones. It is used in the treatment of hyperthyroidism and does not have a role in the treatment of papillary thyroid carcinoma.

Answer C: Radioactive iodine is used as an adjunct after thyroidectomy in the treatment of papillary thyroid carcinoma in order to target any thyroid cells that may remain even after surgical excision. Surgery is the primary therapy for papillary thyroid carcinoma. Radioactive iodine is the primary method of therapy in cases of Grave disease, toxic adenoma, or multinodular goiter.

Answer D: Repeating an ultrasound in 6 months to assess the growth of the nodule or the development of suspicious characteristics is appropriate in cases where the ultrasound and biopsy findings are consistent with a benign thyroid nodule. The ultrasound findings of hypoechogenicity, microcalcifications, hypervascularity, and taller-than-wide nodules suggest malignancy, and together with a biopsy consistent with thyroid malignancy would warrant surgical treatment with subsequent radioactive iodine ablation.

Bullet Summary:
Papillary thyroid carcinoma is managed with thyroidectomy followed by radioactive iodine ablation and long-term levothyroxine to suppress thyroid-stimulating hormone stimulation of any remaining malignant cells.


Question: A 4-day-old neonate is brought to the pediatrician with vaginal discharge for the last 2 days. Her daughter has been feeding and voiding well. The neonate was delivered at 39 weeks gestation via an uncomplicated vaginal delivery and was discharged home after 2 days. The prenatal course was complicated by chlamydia in the mother during the first trimester, for which she and the partner were both treated with a confirmatory test of cure. The biological father is no longer involved in the patient's life, but her mother’s boyfriend has been caring for the baby whenever the mother rests. The neonate’s temperature is 98.5°F (36.9°C), blood pressure is 56/35 mmHg, pulse is 138/min, and respirations are 51/min. She appears comfortable, and cardiopulmonary and abdominal exams are unremarkable. There are no bruises or marks on her skin. Examination of the genitals reveals no vulvar irritation or skin changes but there is scant pink mucoid discharge at the introitus. Which of the following is the most appropriate next step in management?

Answer: Reassurance

Explanation:
This neonate presents with bloody vaginal discharge soon after birth without vulvar irritation, which is most consistent with physiologic neonatal vaginal discharge. Reassurance is the most appropriate next step in management.

Vaginal discharge in a neonate that is bloody and/or mucoid is most commonly due to the rapid withdrawal of maternal hormones that cross the placenta. This results in a pink discharge that may be observed as “menses” in the perinatal period. This most commonly presents several days to 1 week after birth and will self-resolve. Without concerning red flags such as genital trauma, mucopurulent discharge, or surrounding skin changes, there is no need for work-up or treatment. Additional concerning findings should prompt a work-up for child abuse.

Guritzky and Rudnitsky review the evidence regarding the work-up of a bloody neonatal diaper. They discuss how using an Apt test can be helpful in distinguishing between maternal and fetal blood. They recommend being aware of neonatal conditions that can cause bleeding to avoid missing pathologies.

Incorrect Answers:
Answer B: Reporting the case to child protective services would be necessary if child abuse were suspected. Although having an unrelated adult as a caregiver is traditionally a risk factor, there is no evidence that this neonate is being abused. Risk factors include vaginal trauma and bruising.

Answer C: Vaginal culture may be indicated if an infectious etiology such as chlamydia or group A streptococcus is suspected; however, this would more commonly present with bloody and mucopurulent discharge with or without surrounding skin inflammation. Furthermore, the patient’s mother was successfully treated for chlamydia during pregnancy, making chlamydial infection unlikely.

Answer D: Vaginal exam under anesthesia would be appropriate if a foreign body or trauma is suspected because prepubescent children should not undergo exams while awake. In a neonate with physiologic discharge, an exam is unnecessary. Foreign bodies would present with bloody discharge, pain, and potential purulence.

Answer E: Warm water irrigation of the vagina may be helpful in locating a foreign body, which is the most common cause of vaginal bleeding and discharge in a prepubertal girl. This is unlikely in a neonate and there is no evidence of trauma or irritation in the perineum.

Bullet Summary:
Vaginal discharge in a neonate is most commonly due to the withdrawal of maternal hormones and will self-resolve.


Question: A 3-day-old boy is evaluated in the neonatal intensive care unit for failure to pass meconium. The patient is otherwise doing well and feeding every 2 hours. He is urinating 8-10 times per day. The patient has had 2 episodes of vomiting that were described as green in color. He was born at 39 weeks gestation to a 38-year-old G3P3 mother. The pregnancy was uncomplicated, and the patient’s mother received routine prenatal care. She declined prenatal testing. One of the patient’s older siblings has Down syndrome. The patient's temperature is 98.2°F (36.8°C), blood pressure is 48/32 mmHg, pulse is 164/min, and respirations are 48/min. On physical exam, the patient is in no acute distress. His abdomen is firm, non-tender, and distended with hypoactive bowel sounds. A digital rectal exam fails to relieve the obstruction. An abdominal radiograph is performed and the result can be seen in Figure A. Which of the following is the most appropriate next step in management?

Answer: Contrast enema

Explanation:
This patient presents with delayed passage of meconium, bilious emesis, unsuccessful disimpaction on digital rectal exam, and dilated loops of bowel on abdominal radiograph which suggests a diagnosis of meconium ileus. The most appropriate next step in management is an enema with water-soluble contrast which may be both diagnostic and therapeutic.

Meconium ileus presents with bilious emesis and failure to pass meconium in the first 48 hours of life. Abdominal radiography typically shows dilated loops of the small intestine proximal to the obstruction. Enema with water-soluble contrast (Gastrografin) is both diagnostic and therapeutic, as the contrast not only visualizes a microcolon but also relieves the obstruction via the osmotic pull of water into the lumen of the colon. Surgery may be necessary if the contrast enema fails. Patients should also be evaluated for underlying conditions such as cystic fibrosis.

Adams and Stanton review the evidence regarding the diagnosis and treatment of neonatal bowel obstruction. They discuss how malrotation, jejunoileal atresia, duodenal atresia, and colonic atresia are common causes of this finding. They recommend surgical management of these conditions.

Figure/Illustration A is an abdominal radiograph demonstrating dilated loops of bowel and a “soap bubble” appearance of meconium mixed with bowel gas in the right lower quadrant (red circle). These findings are classically seen in patients with meconium ileus.

Incorrect Answers:
Answer A: An abdominal radiograph would be faster but less accurate than an abdominal CT. The use of CT should also be restricted in the pediatric population due to the radiation exposure involved.

Answer C: Rectal suction biopsy is the most accurate test to diagnose Hirschsprung disease, which may present like meconium ileus with bilious vomiting, delayed passage of meconium, and dilated loops of bowel on an abdominal radiograph. A digital rectal exam typically temporarily relieves the intestinal obstruction in Hirschsprung disease and produces an expulsion of gas and stool called the “squirt sign.”

Answer D: Sweat testing is used to diagnose cystic fibrosis, which is strongly associated with meconium ileus. An enema with water-soluble contrast would be the best next step to both confirm the diagnosis and relieve the obstruction. The patient should subsequently undergo sweat testing.

Answer E: Upper gastrointestinal series is the diagnostic test of choice for intestinal malrotation which may also present with bilious vomiting. Malrotation is less likely to present with delayed passage of meconium, and an abdominal radiograph would more likely demonstrate a midgut volvulus. Treatment is with surgical derotation.

Bullet Summary:
Patients with meconium ileus should undergo an enema with water-soluble contrast (Gastrografin) to both confirm the diagnosis and relieve the obstruction.


Question: A 4-week-old boy is brought to the pediatrician by his parents for an initial evaluation. His parents are concerned that he is not feeding well and has lost weight over the last 2 weeks. He was born at home via spontaneous vaginal delivery at 37 weeks of gestation to a G1P1 mother. His mother did not receive prenatal care. His blood pressure is 70/44 mmHg, pulse is 151/min, and respirations are 41/min. His weight is 3 kg (4th percentile) compared with 3.5 kg at birth (45th percentile). On physical exam, he is jaundiced with an enlarged liver and spleen. He does not appear to respond to visual stimuli, and further examination reveals bilateral clouding of the lens. Which of the following interventions could have avoided this patient's symptoms?

Removing phenylalanine from maternal diet during pregnancy

Answer: Changing to a soy based formula

Explanation:
This patient who presents with failure to thrive, hepatosplenomegaly, and bilateral cataracts most likely has classic galactosemia. Patients with this disorder should avoid lactose-containing products by changing to a soy-based formula.

Classic galactosemia is an autosomal recessive defect in galactose-1-phosphate uridyltransferase. This enzyme is involved in the conversion of galactose to glucose, and a deficiency of this enzyme results in the accumulation of galactose 1-phosphate in the liver, kidney, and brain. This metabolite acts as a phosphate sink, meaning that it traps all free phosphate in the cytosol and inhibits the formation of other phosphate-dependent metabolites such as adenosine triphosphate. This results in failure to thrive, vomiting, lethargy, and hepatosplenomegaly after ingestion of galactose-containing products such as milk. Patients will also develop bilateral cataracts if the deficit is not detected in the first few weeks after birth. Avoiding galactose by changing to a soy-based formula will avoid the complications of this disorder.

Turck discusses using soy protein for infant feeding. The author notes that there are safety concerns with regards to the high phyto-estrogenic isoflavone content of these formulas. The author recommends that despite these safety concerns, these formulas should still be used in patients with classic galactosemia.

Incorrect Answers:
Answer A: Avoiding fruit juice and sweetened foods would be effective in the treatment of hereditary fructose intolerance. This disease presents similarly to classic galactosemia, but cataracts would not be seen in patients with this disease.

Answer C: Providing imiglucerase enzyme replacement would be effective in the treatment of patients with Gaucher disease, which can also present with failure to thrive. However, associated findings in this disease would be anemia and avascular necrosis of the bones.

Answer D: Removing phenylalanine from the maternal diet during pregnancy would be effective in the treatment of patients with phenylketonuria, which can also present with failure to thrive. However, these patients classically present with a "musty smell" and eczema.

Answer E: Vitamin B6 supplementation may be effective in mitigating the negative symptoms of homocystinuria. This disease may also present with cataracts or lens dislocations. Associated findings in this disorder would be marfanoid appearance and arachnodactyly.

Bullet Summary:
Patients with classic galactosemia should not be breastfed and should receive a galactose-free and lactose-free diet such as soy-based formulas.


Question: A 4-week-old boy presents with his parents to the pediatrician for a well-child visit. His mother reports he was eating well until 1 week ago when he began vomiting after breastfeeding. His mother has tried increasing the frequency of feeds and decreasing the amount of each feed, but the vomiting seems to be getting worse. The patient now vomits after every feed. The vomitus looks like breast milk. The patient’s mother is exclusively breastfeeding and would prefer not to switch to formula but worries that the patient is not getting the nutrition he needs. Two weeks ago, the patient was in the 75th percentile for weight and 70th for height. He is now in the 60th percentile for weight and 68th percentile for height. His temperature is 98.2°F (36.8°C), blood pressure is 58/37 mmHg, pulse is 144/min, and respirations are 34/min. On physical exam, the patient has dry mucous membranes. His abdomen is soft and non-distended. Which of the following is the most appropriate next step in management?

Answer: Abdominal ultrasound

Explanation:
This patient presents with a history of nonbilious, forceful vomiting, poor weight gain, and signs of dehydration, which is consistent with pyloric stenosis. The most appropriate next step in management is abdominal ultrasound to confirm the diagnosis.

Pyloric stenosis presents in 4- to 6-week-old infants with nonbilious, post-prandial projectile vomiting. Although pyloric stenosis classically presents with an “olive-shaped” mass in the epigastrium, the mass cannot be palpated in some patients. Any infant who develops new, persistent vomiting in the first 2 months of life and has associated dehydration or failure to thrive should undergo an abdominal ultrasound to evaluate for pyloric stenosis. Patients should undergo resuscitation prior to the definitive treatment, which is a pyloromyotomy.

Adams and Stanton review the evidence regarding the diagnosis and treatment of neonatal bowel obstruction. They discuss how malrotation, jejunoileal atresia, duodenal atresia, and colonic atresia are common causes of this finding. They recommend surgical management of these conditions.

Incorrect Answers:
Answer A: Abdominal radiograph is not helpful in evaluating for pyloric stenosis. It is more useful in the workup of bilious vomiting, as several etiologies of bilious vomiting (such as duodenal atresia and Hirschsprung disease) can be seen on an abdominal radiograph. Treatment of these conditions is surgical excision of the defective segment of colon.

Answer C: Supplementing breastfeeding with formula would not be appropriate for this patient as his failure to thrive is driven by gastric outlet obstruction. In the case of pyloric stenosis, formula would cause vomiting just as breastmilk does.

Answer D: A trial of a dairy-free diet is used to improve gastroesophageal reflux, but in the setting of this patient’s age and the description of vomiting, he should undergo an abdominal ultrasound to evaluate for pyloric stenosis. Treatment of reflux also involves positional changes during feeding.

Answer E: A trial of empiric proton pump inhibitor is indicated for patients with gastroesophageal reflux disease, but it would not address this patient’s pyloric stenosis. Patients can also undergo conservative treatments such as changing positioning during feeding.

Bullet Summary:
The diagnostic test of choice for pyloric stenosis in infants is an abdominal ultrasound.


Question: A 25-year-old G1P0 woman presents to her physician for a prenatal visit. She is at 12 weeks gestational age and has not received prior prenatal care. She has mild morning sickness but no other symptoms. She has no known medical problems and takes only a prenatal multivitamin. She has unprotected sexual intercourse with 3 male partners. Her temperature is 98.6°F (37.0°C), blood pressure is 118/70 mmHg, pulse is 80/min, and respirations are 18/min. Physical exam reveals a well-appearing woman in no acute distress. There are no lesions appreciated on skin exam. Cardiopulmonary exam is unremarkable. An antibody test for human immunodeficiency virus (HIV)-1/2 is positive. The patient is started on an appropriate treatment regimen. Assuming that her HIV viral load is undetectable by the time of delivery, which of the following maternal regimens is she most likely receiving and what neonatal prophylaxis is indicated (Figure A)?

Answer: C

Explanation:
This pregnant patient presents with a positive HIV antibody test in the setting of unprotected sexual intercourse. An appropriate maternal HIV treatment regimen is abacavir, lamivudine, and raltegravir; prophylaxis in the infant consists of zidovudine alone if maternal HIV viral load is suppressed to < 50 copies/mL.

All pregnant women should be screened for HIV as early as possible during pregnancy. Maternal treatment for HIV should be initiated as early as possible (before pregnancy if possible) with highly-active anti-retroviral therapy (HAART) consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs) such as abacavir/lamivudine, plus an integrase inhibitor (e.g., raltegravir) or a protease inhibitor (e.g., ritonavir/atazanavir). Regimens for prophylaxis in infants of HIV-positive mothers depends on the HIV viral load at the time of delivery. If the viral load is < 50 copies/mL, infant prophylaxis with zidovudine alone for 4 weeks is sufficient. If the viral load is ≥ 50 copies/mL or the mother did not receive HAART during pregnancy, infant prophylaxis should consist of the 3-drug regimen of: zidovudine, lamivudine, and either nevirapine or raltegravir for 6 weeks.

Harris et al. reviewed the treatment of HIV infection in pregnancy. They found that although anti-retroviral therapy during pregnancy significantly reduces mother-to-child transmission of HIV, it is still associated with certain perinatal complications such as low birthweight and preterm delivery. Despite these risks, they recommend anti-retroviral therapy during pregnancy and during breastfeeding to prevent transmission.

Figure A shows the answer choices.

Incorrect Answers:
Answer A: Maternal treatment with abacavir/lamivudine/raltegravir and no neonatal treatment is inappropriate because all infants of HIV-positive mothers should receive zidovudine (if maternal viral load < 50 copies/mL at delivery). Lamivudine and raltegravir would be added if maternal viral load is ≥ 50 copies/mL at delivery.

Answer B: Maternal treatment with abacavir/lamivudine/raltegravir and neonatal prophylaxis with zidovudine/lamivudine/raltegravir would be appropriate if the maternal viral load were ≥ 50 copies/mL at delivery. The HIV viral load in this patient was assumed to be undetectable at delivery.

Answer D: Maternal treatment with raltegravir/ritonavir/atazanavir and neonatal prophylaxis with zidovudine/lamivudine/raltegravir is inappropriate because raltegravir is an integrase inhibitor and ritonavir/atazanavir are protease inhibitors. HAART must include 2 NRTIs. Atazanavir is often co-administered with ritonavir to increase the former’s bioavailability. Additionally, zidovudine/lamivudine/raltegravir is the neonatal regimen for infants whose mothers have a viral load ≥ 50 copies/mL at delivery.

Answer E: Maternal treatment with raltegravir/ritonavir/atazanavir and neonatal prophylaxis with zidovudine only is inappropriate because HAART for the mother must include 2 NRTIs.

Bullet Summary:
Maternal HIV infection should consist of highly-active anti-retroviral therapy consisting of 2 nucleoside reverse transcriptase inhibitors plus either an integrase inhibitor or protease inhibito, while neonatal prophylaxis consists of zidovudine only for infants of mothers with viral load < 50 copies/mL at delivery.


Question: A 19-year-old woman presents to her primary care physician with headaches, blurry vision, and tinnitus over the past month. She started treatment for a skin condition with a new oral medication 2 months prior. She has not noticed any changes in her complexion as of yet. Her temperature is 98.2°F (36.8°C), blood pressure 100/65 mmHg, pulse 87/min, and respiratory rate 14/min. She is oriented to person, place, and time. Neurological exam reveals papilledema upon examination of both eyes. Skin examination is notable for the findings in Figure A. Which of the following is the most likely diagnosis?

Answer: Idiopathic intracranial hypertension

Explanation:
This young patient with severe nodulocytic acne who was started on a new oral medication (likely isotretinoin) is likely suffering from idiopathic intracranial hypertension, which can present with papilledema, headache, blurry vision, and diplopia.

Idiopathic intracranial hypertension is characterized by an increase in intracranial pressure without an identifiable cause. Patients often present with symptoms that include headache, blurry vision, and tinnitus. Fundoscopic examination typically reveals bilateral papilledema. Vision loss is a complication of this condition with high morbidity. While there is no identifiable cause, common associations include obesity or a recent increase in weight as well as medications such as isotretinoin - a vitamin A derivative that is often used in the management of severe nodulocystic acne vulgaris. Management should first involve imaging of the brain (CT or MRI) to exclude elevated cerebrospinal fluid pressure due to other causes such as brain tumor, dural sinus thrombosis, or hydrocephalus. The diagnosis is made via lumbar puncture revealing increased opening pressure. Lumbar puncture can also result in therapeutic relief. The specimen should be sent for gram stain, culture, and viral PCR to rule out other etiologies. Long term treatment is centered on weight loss and avoiding causative agents. Acetazolamide and serial lumbar punctures are other treatments.

Boyter reviews the clinical presentation and management of patients with idiopathic intracranial hypertension. They found the condition is most common among obese women in their 20's, but it also may occur in children, men, and older adults. They recommend referral for patients to see a neurologist for ongoing management of headaches and other symptoms, as well as an ophthalmologist or neuro-ophthalmologist for monitoring papilledema, given the risk of vision loss.

Figure/Illustration A: The figure depicts a patient with severe nodules and cysts (red arrows) consistent with severe inflammatory nodulocystic acne that would be suitable for treatment with isotretinoin.

Incorrect Answers:
Answer A: Cerebrovascular accidents can be embolic or hemorrhagic in nature and often result in persistent neurologic deficits or resolution of an acute neurologic deficit in a patient with cerebrovascular risk factors (diabetes, hypertension, hyperlipidemia). This young, healthy patient with intermittent headache and neurologic symptoms without a family history of hypercoagulable state is unlikely to have suffered from a cerebrovascular accident.

Answer B: Giant cell arteritis (GCA) is a vasculitis that is typically seen in elderly patients (>60 years of age) and presents with tenderness of the ipsilateral temple and elevated inflammatory markers. Many patients with GCA have one or more constitutional symptoms (weight loss, fever, fatigue, anorexia, malaise) in addition to symptoms such as new onset headache or jaw claudication.

Answer D: Meniere disease affects the inner ear and is characterized by severe episodes of vertigo, tinnitus, hearing loss, and fullness in the ear. Patients are often women between the ages of 40 and 60. Headaches and blurry vision are not a classic part of the clinical presentation.

Answer E: Migraines present with severe headaches that can be incapacitating with associated photophobia and phonophobia. In some cases, patients may present with an aura that precedes or occurs during the migraine. The presence of papilledema suggests elevated intracranial pressure and is not typically seen in migraines.

Bullet Summary:
Idiopathic intracranial hypertension may be a side effect of isotretinoin.


Question: A 1-hour-old newborn boy is evaluated in the delivery room. He was born at 37 weeks gestation to a 39-year-old G3P3 mother. The mother initially labored at home with a midwife but was transferred to the hospital for failure to progress. The infant was eventually delivered via Caesarean section. The mother declined all prenatal screening tests during this pregnancy. His temperature is 98.6°F (37°C), blood pressure is 63/41 mmHg, pulse is 133/min, and respirations are 39/min. His Apgar scores were 7 and 8 at 1 and 5 minutes, respectively. His weight is 3.0 kg (6.6 lb), and his height and his head circumference are in the 30th and 40th percentiles, respectively. On physical exam, he is found to have a 3 cm full-thickness defect in the abdominal wall to the right of the umbilicus with evisceration of a loop of the bowel. The abdominal defect is immediately covered in sterile saline dressings and an orogastric tube and 2 peripheral intravenous lines are placed. This condition is most likely associated with which of the following additional findings?

Answer: A normal cardiac exam

Explanation:
This patient presents with a full-thickness defect in the abdominal wall lateral to the umbilicus with evisceration of the bowel, which suggests a diagnosis of gastroschisis. Gastroschisis is not associated with any cardiac defects.

Gastroschisis and omphalocele are the most common abdominal wall defects found in infants and there are important differences between them. Whereas the eviscerated bowel in gastroschisis is not covered by a membrane, the exposed bowel in the omphalocele is covered by a membranous sac. The abdominal wall defect in gastroschisis is located lateral to the umbilicus, whereas in omphalocele the defect is midline. The distinction is also important for management, as omphalocele is commonly associated with other extraintestinal defects whereas fewer than 10% of cases of gastroschisis are associated with an extraintestinal abnormality. Treatment is with surgical correction of the abdominal wall defect.

Skarsgard reviews the evidence regarding the diagnosis and treatment of gastroschisis. He discusses how this is one of the most common birth defects managed in the ICU setting. He recommends urgent surgical correction.

Incorrect Answers:
Answer B: A bicuspid aortic valve occurs in many cases of Turner syndrome. This disease presents with a webbed neck, short stature, low hairline, broad (“shield”) chest, bicuspid aortic valve, horseshoe kidney, and streak ovaries. Treatment is supportive with surgical fixation of cardiac defects and hormone supplementation with growth hormone.

Answer C: Endocardial cushion defects are most commonly found in trisomy 21 (Down syndrome). Over a third of individuals with trisomy 21 have a complete atrioventricular septal defect, and another third have isolated ventricular septal defects. Infants with Down syndrome commonly present with the upslanting palpebral fissures, flat nasal bridge, transverse palmar crease, and hypotonia. Treatment is with supportive care of these deformities such as surgical correction of cardiac defects.

Answer D: Tetralogy of Fallot is most often associated with trisomy 21 (Down syndrome) and 22q11 deletion syndromes. Infants with Down syndrome commonly present with upslanting palpebral fissures, flat nasal bridge, transverse palmar crease, and hypotonia. Treatment is with supportive care of these deformities such as surgical correction of cardiac defects.

Answer E: Ventricular septal defects occur in several genetic syndromes, including trisomy 21 (Down syndrome) and trisomy 13 (Patau syndrome). Infants with trisomy 13 commonly present with cleft lip or palate, polydactyly, and severe intellectual disability. This disease is not compatible with survival past 1 year of age so treatment can involve termination of pregnancy or supportive care.

Bullet Summary:
Gastroschisis presents with an abdominal wall defect with evisceration of the bowel that is lateral to the umbilicus and is not usually associated with other birth defects.


Question: A 53-year-old African-American woman presents to her primary care doctor with increasing difficulty climbing the stairs. She noticed the weakness approximately 3 months ago. It has gotten progressively worse since that time. She has also noticed increasing difficulty combing her hair, standing from a seated position, and experiences muscle aches. Her medical history is significant for hypertension treated with lifestyle modification and gastroesophageal reflux disease (GERD). Her temperature is 98.6°F (37.0°C), blood pressure is 130/65 mmHg, pulse is 80/min, and respirations are 16/min. She has 3/5 strength to shoulder abduction and hip flexion bilaterally. Her strength is 5/5 to wrist extension and ankle plantar flexion. No skin rashes are noted. Which of the following is the most accurate test to confirm this patient’s diagnosis?

Answer: Muscle biopsy

Explanation:
This patient with insidious, subacute, progressive, symmetric proximal muscle weakness (difficulty climbing the stairs, combing her hair, standing from a seated position) without associated skin lesions most likely has polymyositis. The most accurate diagnostic test for polymyositis is muscle biopsy.

Polymyositis is caused by an autoimmune reaction that leads to cell-mediated cytotoxicity against unidentified skeletal muscle antigens, primarily affecting the endomysium. It is more often found in women, patients between 30-60 years of age, and African-Americans. Clinical features of polymyositis include symmetric proximal muscle weakness that may be accompanied by myalgia, dysphagia (due to pharyngeal muscle weakness), restrictive lung disease (due to respiratory muscle weakness), cardiac involvement (myocarditis, heart failure), interstitial lung disease, and increased risk of malignancy. There are no accepted diagnostic criteria for polymyositis; however, diagnosis is usually secured with a combination of clinical features and other tests. Routine initial studies can include a complete blood count, complete metabolic panel, C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, aldolase, creatine kinase, autoantibodies (anti-nuclear antibody, anti-Jo-1), and electromyography (EMG). Muscle biopsy of an affected muscle is the gold standard for diagnosis and will typically show muscle fiber damage, CD8+ T cells in the endomysium, and overexpression of MHC-I on the sarcolemma. First-line treatment of polymyositis includes glucocorticoids and a steroid-sparing agent (methotrexate, azathioprine). Subsequent treatments can include intravenous immunoglobulins, rituximab, or plasmapheresis.

Amato et al. review the evaluation and treatment of inflammatory myopathies such as polymyositis, dermatomyositis, and inclusion body myositis. They found that polymyositis typically presents in adult life with symmetric proximal leg greater than arm weakness. They recommend that a muscle biopsy be done on any patient considered to have polymyositis, preferably prior to starting immunosuppressive treatment.

Incorrect Answers:
Answer A: Electromyography (EMG) can help distinguish myopathic weakness (e.g., polymyositis) from neuropathic causes of weakness (e.g., amyotrophic lateral sclerosis, myasthenia gravis). Characteristic EMG findings include fibrillations, early recruitment of motor unit potentials, and abnormal low-amplitude motor unit potentials. EMG is not a confirmatory test and is less sensitive than muscle biopsy for diagnosing myositis.

Answer B: MRI can be used to demonstrate areas of edema, atrophy, fatty replacement, and calcification in patients with suspected polymyositis. MRI can assess large regions of muscle, thus avoiding sampling error with muscle biopsy. The findings in MRI are nonspecific and require correlation with muscle biopsy for definitive diagnosis. MRI can also be used to help select the site of muscle biopsy.

Answer D: Serum aldolase can occasionally be used in the diagnostic investigation of suspected polymyositis if creatine kinase is normal. Aldolase elevation is nonspecific and may be seen in fasciitis, drug-induced myositis, and connective tissue disease-associated interstitial lung disease.

Answer E: Serum creatine kinase (CK) is the most sensitive muscle enzyme exam and should be part of the initial diagnostic investigation of any patient with suspected polymyositis. CK elevation is nonspecific and may be seen in myriad conditions such as inflammatory insult, metabolic injury, drug-induced injury, and infection.

Bullet Summary:
Muscle biopsy is the gold standard for the diagnosis of polymyositis.


Question: A 4-week-old boy presents to the pediatrician for vomiting. The patient is breastfed and typically feeds for 20-30 minutes every 2 hours. One week ago, he began vomiting and regurgitating breastmilk through his nose after most feedings. His stools over the past week have also become blood-streaked. The patient does not seem to be in any distress when he passes these bloody stools. The patient surpassed his birth weight by 2 weeks of age but has fallen 1 standard deviation on the growth curve since then. His temperature is 98.6°F (37°C), blood pressure is 78/47 mmHg, pulse is 115/min, and respirations are 28/min. On physical exam, the patient is well-appearing. His face and back have the physical exam finding seen in Figure A. The patient’s abdomen is soft, non-tender, and non-distended. A digital rectal exam reveals a small amount of blood in the rectal vault. Which of the following is the most appropriate next step in management?

Answer: Modify mother's diet

Explanation:
This infant presents with vomiting, bloody stools, and poor weight gain, which suggests a diagnosis of milk-protein allergy. The most appropriate next step in management is the modification of the mother’s diet to eliminate cow’s milk and soy.

Infant food protein-induced proctocolitis is caused by distal colon inflammation secondary to an immune reaction to certain food proteins. Milk-protein allergy is the most common food allergy in children and presents with vomiting, bloody stools, and poor weight gain or failure to thrive. In an infant that is breastfed, the most appropriate next step in management is the elimination of cow’s milk and soy from the mother’s diet. In an infant who is formula fed, the most appropriate next step would be switching to either an extensively hydrolyzed or amino acid-based infant formula.

Giannetti et al. review the evidence regarding the diagnosis and treatment of milk protein allergy in infants. They discuss how the selective elimination of certain proteins from the diet is usually effective. They recommend considering oral immunotherapy as an adjuvant in the treatment of this disease.

Figure/Illustration A is a clinical photograph that demonstrates the finding of eczema (red circle). This finding is commonly found in patients with milk-protein allergy.

Incorrect Answers:
Answer A: Initiating a proton pump inhibitor would be appropriate in patients with refractory gastroesophageal reflux disease, which presents with regurgitation or vomiting and symptoms of feeding aversion or failure to thrive. Because this patient presents with bloody stools, he is more likely to have a milk protein allergy.

Answer B: Obtaining an abdominal ultrasound would help evaluate for pyloric stenosis, which presents in infants between 3-6 months of age with non-bilious, projectile vomiting. Pyloric stenosis does not cause bloody stools. Treatment is with surgical pyloromyotomy.

Answer C: Providing reassurance would not be appropriate for an infant presenting with bloody stools and evidence of poor weight gain. The cause of his blood-streaked stools should be investigated to ensure this patient is getting the nutrition he needs.

Answer E: Switching to a hydrolyzed formula would be appropriate if this patient were formula fed, but it is not necessary to discontinue breastfeeding if the mother is willing to modify her diet to exclude cow’s milk and soy.

Bullet Summary:
A milk-protein allergy in a breastfed infant should be treated with modification of the mother’s diet to eliminate cow’s milk and soy.