Question: A 46-year-old farmer presents to the office for a follow-up visit. He was seen 4 days ago for a new lesion on his arm that had been present for 1 week prior to that visit. A photograph of the lesion is shown in Figure A. At that time, he was prescribed treatment for the lesion and instructed to follow up as necessary. Today, he reports that he became sunburned this morning within an hour of beginning his workday, despite wearing appropriate sunscreen. He has a medical history significant for type 2 diabetes mellitus that is controlled with metformin. He has no known medical allergies. He smokes 1 pack of cigarettes per day and denies alcohol or illicit drug use. His temperature is 98.6°F (37.0°C), blood pressure is 125/70 mmHg, pulse is 65/min, and respirations are 12/min. On exam, there is a blistering erythematous rash on the arms and shoulders. The previous skin lesion appears unchanged. Which of the following is the most likely explanation for the patient's new rash?

Progression of disease and surgical debridement is necessary

Answer: Adverse effect of doxycycline

Explanation:
This farmer has a cutaneous black eschar most consistent with cutaneous anthrax for which doxycycline is an appropriate treatment. A new blistering, erythematous rash after spending an hour outside that appears 4 days after starting treatment is consistent with a photosensitivity reaction, a known adverse effect of doxycycline.

Cutaneous anthrax is the most common form of infection caused by Bacillus anthracis. The infection is contracted during contact with infected livestock. The first-line treatment is doxycycline, ciprofloxacin, levofloxacin, or moxifloxacin. Progression to systemic anthrax would result in pulmonary (flu-like symptoms and hemoptysis) or gastrointestinal (nausea, vomiting, and dysentery) symptoms and would require treatment with clindamycin plus ciprofloxacin. Patients with meningitis due to anthrax require antibiotic therapy with ciprofloxacin plus meropenem plus linezolid. Additionally, antitoxins such as raxibacumab and adjunctive therapies such as glucocorticoids should be considered. In addition to photosensitivity, adverse effects of doxycycline include gastrointestinal upset (most common), teeth discoloration, and inhibition of bone growth in children. Doxycycline is teratogenic and should not be prescribed during pregnancy.

Migone et al. discuss the use of raxibacumab, a monoclonal antibody against a component of the anthrax toxin, in treating inhalational anthrax. The authors found that in monkeys, raxibacumab significantly increased survival after exposure to anthrax. The authors recommend the use of antitoxins such as raxibacumab in any patient suspected of having systemic anthrax.

Figure/Illustration A demonstrates the characteristic black eschar (blue circle) of cutaneous anthrax.

Incorrect Answers:
Answer A: Adverse effects of ciprofloxacin do not include photosensitivity, though it is an appropriate antibiotic choice for cutaneous anthrax treatment. Adverse effects of ciprofloxacin include gastrointestinal upset, risk of tendon rupture, and QT prolongation.

Answer C: Allergic reactions to prescribed therapy would be characterized by urticaria and wheals. In severe cases, anaphylaxis may be present.

Answer D: Progression of disease and alternative therapy is indicated does not fit this case. The patient's symptoms (blistering, erythematous rash) are not concerning for the progression of cutaneous anthrax to systemic disease, which would result in pulmonary or gastrointestinal symptoms. Alternative therapy for systemic anthrax is not indicated in this case.

Answer E: Progression of disease and surgical debridement is not indicated. The patient's symptoms (blistering, erythematous rash) are not concerning for the progression of cutaneous anthrax to systemic disease, which would result in pulmonary or gastrointestinal symptoms. Additionally, surgical debridement is not indicated for cutaneous anthrax.

Bullet Summary:
Cutaneous anthrax presents with a black eschar and is treated with antitoxin and either doxycycline or ciprofloxacin, the former of which can cause a photosensitivity reaction.


Question: A 16-year-old boy presents to an ophthalmologist with blurry vision. Over the past several months, he has had increasing difficulty seeing the board from the back of the classroom at school. The patient is otherwise doing well in school and enjoys playing basketball. His medical history is otherwise significant for scoliosis which is managed by an orthopedic surgeon. His family history is significant for a mother with type 2 diabetes mellitus and a father who underwent aortic valve replacement last year. His temperature is 98.6°F (37°C), blood pressure is 115/71 mmHg, pulse is 72/min, and respirations are 12/min. On physical exam, the patient is tall for his age and has long arms. He has 20 degrees of thoracic scoliosis, which is stable from previous exams. On slit-lamp examination, the patient is found to have bilateral upward lens subluxation and is prescribed corrective lenses. Which of the following is the most likely cause of this patient’s symptoms?

Answer: Mutation of chromosome 15

Explanation:
This patient presents with tall stature, upward lens subluxation, and a family history of aortic valve disease, which suggests a diagnosis of Marfan syndrome. Marfan syndrome is caused by an autosomal dominant mutation in the fibrillin-1 gene on chromosome 15.

The fibrillin-1 gene codes for a glycoprotein in the extracellular matrix of connective tissue. Patients with Marfan syndrome classically present with a triad of musculoskeletal, ocular, and cardiovascular symptoms. The musculoskeletal findings include tall stature, long limbs, arachnodactyly, pectus excavatum, joint hypermobility, skin hyperelasticity, and scoliosis. Patients with Marfan syndrome also often present with upward lens subluxation, and they are at increased risk of cardiac disease, including aortic regurgitation and aortic dissection. Treatment is symptomatic with avoidance of contact sports, beta-blockers, and valve repair to prevent cardiac complications.

Bitterman and Sponseller review the evidence regarding the diagnosis and treatment of Marfan syndrome. They discuss how skeletal manifestations are often the initial presentation of this condition leading to diagnosis. They recommend screening for patients who are suspected to have this disease.

Incorrect Answers:
Answer A: Defective metabolism of methionine describes homocystinuria, an autosomal recessive deficiency of cystathionine synthase. Although patients with homocystinuria may also have tall stature, arachnodactyly, and pectus deformity, the lens dislocation in homocystinuria is downward rather than upwards. Patients with homocystinuria also tend to have a fair complexion, intellectual disability, and thrombophilia. Treatment includes vitamin B6 supplementation.

Answer B: Extra copy of a sex chromosome describes Klinefelter syndrome (47,XXY). Although patients with Klinefelter syndrome classically present with tall stature, they do not have the other clinical features found in this patient, including joint hypermobility and lens subluxation. Patients with Klinefelter also present with hypogonadism and azoospermia. Treatment is supportive

Answer D: Mutation of COL5A1 or COL5A2 leads to Ehlers-Danlos syndrome, a collagen disorder that commonly presents with joint hypermobility, skin hyperextensibility, and skin fragility with easy bruising. Ehlers-Danlos would not explain this patient’s lens subluxation. Treatment may include bracing of unstable joints.

Answer E: Mutation of RET proto-oncogene describes multiple endocrine neoplasia type 2B (MEN2B). Patients with MEN2B may present with Marfanoid habitus and are predisposed to medullary thyroid cancer, pheochromocytoma, and mucosal neuromas. MEN2B would not explain lens subluxation. Treatment is with surgical resection of tumors.

Bullet Summary:
Marfan syndrome is caused by an autosomal dominant mutation in the fibrillin-1 gene on chromosome 15 and presents with a triad of musculoskeletal, ocular, and cardiovascular findings.


Question: A 62-year-old man presents to the emergency department with increased fatigue and changes in his vision. For the past month, he has felt abnormally tired and today noticed his vision is blurry. The patient also endorses increased sweating at night and new-onset headaches. He currently feels dizzy. The patient has a medical history of diabetes and hypertension. His current medications include insulin, metformin, and lisinopril. His temperature is 99.5°F (37.5°C), blood pressure is 157/98 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 98% on room air. A cardiopulmonary exam is within normal limits. HEENT exam reveals non-tender posterior and anterior chain lymphadenopathy. Abdominal exam reveals splenomegaly and hepatomegaly. There are large, non-tender palpable lymph nodes in the patient's inguinal region. A neurological exam is notable for decreased sensation in the patient's hands and feet. He also complains of numbness and tingling pain in his extremities that has been persistent during this time. The dermatologic exam is notable for multiple bruises on his upper and lower extremities. Which of the following is most likely to be abnormal in this patient?

Answer: IgM

Explanation:
This patient is presenting with symptoms of hyperviscosity, fatigue, and organomegaly suggestive of a diagnosis of Waldenstrom macroglobulinemia (WM). WM is characterized by increased IgM production.

WM occurs secondary to a clonal B-cell that pathologically overproduces IgM. High levels of IgM can lead to symptoms of hyperviscosity including blurred vision, dizziness, headaches, and peripheral neuropathy. Organomegaly is a unique finding in WM and can present with hepatomegaly and splenomegaly. Other non-specific findings include fatigue, anemia, and lymphadenopathy. This disease can be diagnosed using protein electrophoresis, which would demonstrate a spike in the levels of IgM protein. Treatment can include plasmapheresis and rituximab.

Gertz et al. review the evidence regarding the diagnosis and treatment of patients with WM. They discuss how patients often present with organomegaly as well as symptoms of hyperviscosity. They recommend rituximab treatment in symptomatic patients.

Incorrect Answers:
Answers 1 & 2: Calcium and IgA/IgG can be elevated in multiple myeloma (MM). MM presents with fatigue, weight loss, bone pain (back pain in particular), and other non-specific findings. MM less commonly presents with symptoms of hyperviscosity and organomegaly and this phenomenon has been described primarily with the IgA subtype. This is a late phenomenon and would be unlikely without preceding symptoms of bone pain and weight loss as a substantial protein concentrations (>5 g/dL) are required for this phenomenon. Treatment is with systemic chemotherapeutic agents.

Answers 4 & 5: Natural killer cells and T-cells could be elevated in non-Hodgkin lymphoma which would present with fatigue, lymphadenopathy, and "B-symptoms" (e.g., night sweats and chills). It would not present with symptoms of hyperviscosity. Treatment is with multi-agent chemotherapy as well as possible local radiation therapy.

Bullet Summary:
Waldenstrom macroglobulinemia (hyper IgM syndrome) presents with symptoms of hyperviscosity, fatigue, and organomegaly.


Question: A 26-year-old medical student presents to occupational health after sustaining a needlestick injury. She was drawing blood from an HIV-positive patient when she stuck herself percutaneously while capping the needle. She immediately washed the puncture wound with saline. The medical student has had a negative HIV serology from the beginning of medical school 2 years ago. She is monogamous with one male partner and denies any intravenous drug use. The source patient was recently diagnosed with HIV and has a CD4 count of 550 cells/µL. His most recent viral load is 1,800,000 copies/mL, and he was started on HAART 3 days ago. Which of the following is the most appropriate next step in management?

Immediately initiate triple antiretroviral therapy

Repeat HIV serology and initiate triple antiretroviral therapy if negative

Repeat HIV serology and initiate triple antiretroviral therapy if positive

Repeat HIV serology and initiate triple antiretroviral therapy immediately

Answer: Repeat HIV serology and initiate triple antiretroviral therapy immediately

Explanation:
This medical student has sustained a hollow-bore needlestick injury. The most appropriate next step is to repeat HIV serology and immediately initiate triple antiretroviral therapy with tenofovir, emtricitabine, and raltegravir.

Healthcare exposures to HIV are divided into 2 categories based on the level of contact with the source patient. If the healthcare worker’s mucous membrane or nonintact skin comes into contact with an HIV-positive patient’s blood, semen, or vaginal secretions, immediate prophylaxis is recommended. This category also includes all needlestick exposures. If the healthcare worker’s mucous membrane or nonintact skin comes into contact with an HIV-positive patient’s urine, feces, or bodily secretions, prophylaxis is not recommended. If the source patient’s HIV status is unknown, it should be assumed that the patient is HIV positive until testing proves otherwise. The triple antiretroviral drug combination of tenofovir, emtricitabine, and raltegravir is favored due to the low incidence of side effects. Prophylactic treatment should be initiated immediately (ideally within 1-2 hours) and continued for 4 weeks at which time the healthcare worker’s serology should be repeated.

Parikh et al. studied technologies for monitoring HIV infection. They discuss how high throughput methods are required in order to surveil for infection on a population level. They recommend using next-generation sequencing methods to improve surveillance methods.

Incorrect Answers:
Answer A: Immediately initiating triple antiretroviral therapy is appropriate after drawing the medical student’s HIV serology. The patient’s serology at the time of exposure must be established to compare to future testing. Despite her previous negative serology and low-risk lifestyle, it would still be best to repeat the testing at the same time prophylactic treatment is initiated.

Answer B: Perform genotype testing on source patient and initiate antiretroviral therapy tailored to results is incorrect because this option would delay the initiation of prophylaxis. Empiric treatment with a triple antiretroviral drug combination is appropriate for all patients with high-risk exposure.

Answer C: Waiting to hear that the medical student’s HIV serology is negative would delay the initiation of prophylaxis. Triple antiretroviral drug treatment should be initiated without waiting for the results. Empiric treatment of all patients with high-risk exposure is recommended in all cases.

Answer D: Waiting for the results of the medical student’s serology would delay treatment for her exposure. If her serology is already positive, she will need to be treated past the 4-week period of prophylaxis. Even though she does not engage in high-risk behaviors, a positive serology would demonstrate that she was already infected with HIV.

Bullet Summary:
After a needlestick injury from a HIV-positive source patient, a healthcare worker’s HIV serology should be drawn and they should be immediately initiated on triple antiretroviral drug therapy.


Question: A 51-year-old man presents to the emergency department complaining of fever and a cough with yellow-green sputum for the past 3 days. He denies any hemoptysis, facial pain, rhinorrhea, or night sweats. The patient reported similar symptoms 2 months ago. Chest radiograph performed at the time was notable for a right middle lobe consolidation. He was diagnosed with lobar pneumonia and completed a 7-day course of antibiotics with complete resolution of his symptoms. He has no other significant medical history and does not take any medications. He has smoked 1 pack of cigarettes a day for 35 years and drinks 3 beers per week. He is sexually active with his wife. His temperature is 101.7°F (38.7°C), blood pressure is 127/85, pulse is 102/min, and respirations are 22/min. Physical exam is notable for decreased breath sounds on the right side without wheezing and increased dullness to percussion on the right side. A chest radiograph is ordered and reveals a consolidation in the right middle lobe. Which of the following is the most appropriate next step in management?

Human immunodeficiency virus (HIV) antibody assay

Answer: CT of the chest without contrast

Explanation:
This patient's presentation with recurrent pneumonia in the same anatomical location is concerning for an anatomic abnormality. Given his history of heavy smoking, lung cancer should be ruled out with a chest CT with possible subsequent bronchoscopy for tissue biopsy.

Recurrent pneumonia can be classified either as those confined to 1 anatomical location of the lung or those involving different portions of the lung. If recurrent pneumonia is limited to a single region, the patient should be evaluated for an anatomic obstruction, such as a mass or mucous plug. Obstruction will hinder mucociliary clearance and allow for the proliferation of bacteria, leading to recurrent infections. The most concerning etiology of such an obstruction is a tumor causing external bronchial compression. Thus, patients should be screened with a chest CT to rule out lung cancer in these cases. If lesions are identified on CT, subsequent bronchoscopy or CT-guided biopsy may be warranted. Treatment may involve radiotherapy, chemoimmunotherapy, or surgery depending on the underlying malignancy. Other causes of recurrent pneumonia limited to an anatomical region include recurrent aspiration secondary to tracheoesophageal disorders or seizures.

Purysko et al. discuss the role of contrast enhancement in chest CTs. The authors find common indications for contrast-enhanced chest CTs include investigation for pulmonary embolism, pleural pathology, or hilar pathology. The authors recommend against the regular use of contrast enhancement in chest CTs outside of selected indications as they rarely provide additional diagnostic benefits while subjecting the patient to the risk of adverse effects with contrast agents.

Incorrect Answers:
Answer A: Barium swallow is often done to investigate anatomical abnormalities of the upper gastrointestinal tract such as tracheoesophageal fistula or Zenker diverticulum. These can increase the risk of aspiration and lead to recurrent pneumonia. In a patient with positive risk factors for cancer, chest CT to rule out malignancy would be the most appropriate next step.

Answer C: Human immunodeficiency virus (HIV) can cause secondary immunodeficiency, which can predispose patients to recurrent infections. These recurrent pneumonias would be expected to be in different regions of the lung and not anatomically confined.

Answer D: Interferon-gamma release assay can be used to diagnose tuberculosis (TB). Reactivation of TB will present clinically with fever, cough, hemoptysis, and night sweats. Chest radiography will commonly reveal an upper lobe infiltrate.

Answer E: Serum immunoglobulin levels would be an appropriate next step to diagnose primary immunodeficiencies such as common variable immunodeficiency or other antibody defects. This would present with multiple lung infections in different regions of the lung. Moreover, these patients would be expected to have other infections such as sinusitis, otitis, and gastrointestinal infections.

Bullet Summary:
Recurrent pneumonia in the same anatomical region should be worked up with a CT with subsequent bronchoscopy and biopsy to rule out malignancy.


Question: A 15-year-old boy is brought to his pediatrician for a follow-up visit. His parents report that he is doing well in school and has many friends. Their only concern is that he has a “difficult stomach.” Every few months, he complains of intermittent abdominal pain that takes several days to pass. He occasionally misses school due to the pain. There is blood in his stool during these episodes. These symptoms have persisted for many years. The parents have so far managed the condition using herbal teas and essential oils but have not sought formal medical care. His temperature is 98.2°F (36.8°C), blood pressure is 106/61 mmHg, pulse is 88/min, and respirations are 12/min. He has lost 10 pounds since his annual visit the year before and is the same height. On physical exam, the patient is thin with conjunctival pallor. His sclerae are anicteric and his abdomen is soft and non-tender without hepatosplenomegaly. He also has the findings seen in Figure A. He undergoes an abdominal CT that shows disease affecting the terminal ileum. Which of the following is most likely to be present in this patient?

Increased serum methylmalonic acid level

Answer: Increased serum methylmalonic acid level

Explanation:
This patient with episodic abdominal pain, bloody stool, growth failure, and erythema nodosum most likely has Crohn disease. Disease involving the terminal ileum predisposes patients to vitamin B12 deficiency, which would cause anemia with an elevated serum methylmalonic acid level.

Crohn disease is an inflammatory bowel disease that presents with abdominal pain, bloody stools, and growth failure in children. Extra-intestinal manifestations of Crohn disease include fistula formation and erythema nodosum, which appear as multiple tender erythematous nodules that fade after 1-2 weeks into bluish plaques or macules that can be confused with bruises. Complications of Crohn disease when the disease involves the terminal ileum is vitamin deficiency and malabsorption. These deficiencies can include vitamin A, vitamin D, vitamin E, vitamin K, zinc, and vitamin B12. Vitamin B12 deficiency presents with a macrocytic, megaloblastic anemia with hypersegmented neutrophils on peripheral blood smear. Lab findings include elevated serum homocysteine and methylmalonic acid levels. Vitamin B12 deficiency is also associated with peripheral neuropathy and should be treated with intramuscular vitamin repletion.

Akbulut presents the current state of evidence regarding vitamin deficiency in patients with Crohn disease. They found that vitamin B12 and folate levels are often low in patients with this disease. They recommend monitoring vitamin levels and providing repletion when necessary.

Figure/Illustration A is a clinical photograph showing erythematous nodules on the extensor surfaces of the legs (red circles). This finding is consistent with the latter stage of erythema nodosum.

Incorrect Answers:
Answer A: Decreased mean corpuscular volume may be seen in iron deficiency anemia, which can be co-morbid with Crohn disease. While this patient does have recurrent gastrointestinal blood loss, the very low frequency of his symptoms is unlikely to result in iron deficiency, making a decreased MCV less likely compared to an increased MCV given the underlying terminal ileum pathology.

Answer B: Decreased serum homocysteine level is not seen in any common human disease. An elevated (not decreased) serum homocysteine level is seen in vitamin B12 deficiency in addition to folate deficiency. This increase is due to the impaired processing of homocysteine in the absence of these cofactors.

Answer D: Microcytes would not be seen in vitamin B12 deficiency or folate deficiency, which instead present with macro-ovalocytes. Microcytic anemia would be seen in patients with iron deficiency anemia, which can present with fatigue and pallor in patients with occult bleeding. Iron supplementation and treatment of the underlying source of bleeding is appropriate care.

Answer E: A prolonged PTT could be seen in this patient as vitamin K absorption is likely affected. This patient is not presenting with a chief complaint of bruising/bleeding (the physical exam finding is erythema nodosum rather than ecchymosis), and symptoms point toward a diagnosis of anemia which would be associated with poor B12 absorption.

Bullet Summary:
Crohn disease may affect the terminal ileum, resulting in vitamin B12 deficiency (increasing the serum methylmalonic acid level) that would present with macrocytic, megaloblastic anemia with hypersegmented neutrophils on a peripheral blood smear.


Question: A 55-year-old woman presents to the emergency department for evaluation of headache. She had a headache that was present for a few hours before subsiding 2 days ago, and then today she developed a headache that was sudden in onset and at maximal intensity within minutes. She has never had a headache like this in the past. Her temperature is 99.0°F (37.2°C), blood pressure is 157/99 mmHg, pulse is 90/min, respirations are 16/min, and oxygen saturation is 99% on room air. On exam, she has pain with passive and active movement of the neck. No focal neurologic deficits are appreciated. A non-contrast head CT is obtained as shown in Figure A. Which of the following is the most likely underlying etiology of this patient's headache?

Answer: Rupture of a berry aneurysm

Explanation:
This patient with sudden-onset headache, neck pain, and a CT scan showing blood in the basal cisterns likely has a subarachnoid hemorrhage. The most common cause of non-traumatic subarachnoid hemorrhage (SAH) is rupture of a saccular (berry) aneurysm.

SAH typically presents with a sudden onset "thunderclap" headache that is often described as the "worst headache of my life." Hypertension is a common risk factor. The diagnosis can be confirmed with a non-contrast head CT. Non-contrast CT scan of the head is sufficient to rule out subarachnoid hemorrhage if performed within 6 hours of symptom onset. If the head CT is negative but SAH is still suspected, a lumbar puncture can help confirm the diagnosis (demonstrating xanthochromia) or CT angiography can be performed. Patients should be admitted for neurosurgery and neuro-IR consultation and may require calcium channel blockers and possible intervention.

Macdonald et. al review spontaneous subarachnoid hemorrhage. They discuss the pathophysiology, clinical manifestations, and diagnosis. They note the typical finding of accumulation of blood in the basal cisterns and sylvian fissures on CT imaging.

Figure A shows a non-contrast head CT demonstrating blood in the subarachnoid space supporting the diagnosis of SAH. Note the hyperdensity in the sylvian fissures and basal cisterns.

Incorrect Answers:
Answer A: CNS vascular endothelial dysfunction results in posterior reversible encephalopathy syndrome, which typically presents with hypertension and encephalopathy.

Answer B: Dehydration and stress could explain a migraine headache or a tension headache. Migraine headaches are often pulsating and may be associated with aura.

Answer C: Hypersensitivity of the trigeminal nerve is thought to be involved in the pathophysiology of migraine headache, and also could describe trigeminal neuralgia which presents with sudden and severe electrical pain in the distribution of the trigeminal nerve with minor stimulation.

Answer D: Muscular pain and strain describes a tension headache which presents with diffuse head pain that is mild and not localized. CT imaging is normal in tension headache.

Bullet Summary:
Spontaneous subarachnoid hemorrhages are most commonly caused by rupture of a berry aneurysm.


Question: A 55-year-old man presents with a 2-day history of mono-articular joint pain. He is otherwise healthy and denies fever, chills, or recent trauma. His medical history is notable for a kidney stone 6 months ago. He underwent a dental procedure to extract an infected wisdom tooth 3 weeks ago. The patient does not take any medications. He is a non-smoker and does not drink alcohol or use recreational drugs. His family history is significant for osteoarthritis in his father who is 78. His temperature is 98.6°F (37°C), blood pressure is 133/84 mmHg, pulse is 84/min, and respirations are 15/min. His body mass index is 27 kg/m^2. Physical examination shows a swollen and tender joint with overlying erythema. Diagnostic arthrocentesis is performed and shows a leukocyte count of 30,000/mm^3 with 85% neutrophils. Polarized microscopy of the synovial fluid is shown in Figure A. Which of the following would most likely be found on this patient’s radiograph?

Answer: Chondrocalcinosis

Explanation:
This patient is presenting with a joint aspiration positive for calcium pyrophosphate dehydrate crystals, suggesting a diagnosis of pseudogout, which may show chondrocalcinosis on radiography.

Pseudogout presents classically with mono- or oligo-articular arthritis that most often affects the knee and proximal joints of elderly patients (> 60 years of age). The disease can be associated with hyperparathyroidism, Gitelman syndrome, familial hypocalciuric hypercalcemia, and hemochromatosis. The patient will have a leukocyte count < 50,000/mm^3 on joint aspiration and positively birefringent, rhomboid-shaped cells on microscopy, which represent calcium pyrophosphate dehydrate (CPPD) crystals. On radiography, chondrocalcinosis can be found, which is the calcification of adjacent cartilaginous structures. Treatment is with indomethacin.

Sidari and Hill review the evidence regarding the diagnosis and treatment of gout and pseudogout. They discuss how diagnosis can be made with fluid microscopy. They recommend treatment with non-steroidal anti-inflammatory drugs.

Figure/Illustration A is polarized microscopy of joint fluid showing rhomboid-shaped crystals that are positively birefringent (red circles). These represent calcium pyrophosphate dehydrate crystals seen in pseudogout.

Incorrect Answers:
Answer A: Boutonniere deformity is characterized by proximal interphalangeal (PIP) joint flexion and distal interphalangeal (DIP) joint extension and is a common hand deformity of rheumatoid arthritis. Rheumatoid arthritis is characterized by insidious onset of morning stiffness and pain that usually affects symmetric PIP and metacarpophalangeal (MCP) joints first. On joint aspiration, leukocyte count ranges from 5,000-50,000/mm^3, but rheumatoid arthritis would not explain the CPPD crystals. Treatment may include methotrexate.

Answer C: Heberden nodes are bony protuberances in the DIP joints, which are characteristic of osteoarthritis. Osteoarthritis presents with insidious onset of joint pain that worsens with activity and weight-bearing. On joint aspiration, the leukocyte count is < 2,000/mm^3.

Answer D: Juxta-articular osteoporosis is decreased bone density of the bone surrounding the joint space. It is a nonspecific sign that can be seen with many inflammatory joint diseases such as rheumatoid arthritis or septic arthritis. Septic arthritis presents with mono-articular joint pain, erythema, and swelling. Joint aspiration will show a leukocyte count > 50,000/mm^3 and Gram stain may be positive.

Answer E: Tophi are deposits of urate crystals in the soft tissue, which are nearly pathognomonic for gout. Gout presents as acute, mono-articular joint pain with physical examination showing a red, inflamed joint (usually the first metatarsophalangeal, knee, or ankle joint). Needle-shaped, negatively birefringent urate crystals are seen in the joint fluid aspirate. Prevention may include allopurinol.

Bullet Summary:
Pseudogout is associated with positively birefringent, rhomboid-shaped crystals and chondrocalcinosis.


Question: A 1-year-old girl is brought to a neurologist due to increasing seizure frequency over the past 2 months. She recently underwent a neurology evaluation which revealed hypsarrhythmia on electroencephalography (EEG) with a mix of slow waves, multifocal spikes, and asynchrony. Her parents have noticed the patient occasionally stiffens and spreads her arms at home. She was born at 38-weeks gestational age without complications. She has no other medical problems. Her medications consist of lamotrigine and valproic acid. Her temperature is 98.3°F (36.8°C), blood pressure is 90/75 mmHg, pulse is 94/min, and respirations are 22/min. Physical exam reveals innumerable hypopigmented macules on the skin and an irregularly shaped, thickened, and elevated plaque on the lower back. Which of the following is most strongly associated with this patient's condition?

Answer: Cardiac rhabdomyoma

Explanation:
This patient with a seizure disorder, ash-leaf spots (innumerable hypopigmented macules), Shagreen patch (elevated irregular plaque on the lower back), and West syndrome (hypsarrhythmia on EEG and movements consistent with infantile spasms) likely has tuberous sclerosis. Tuberous sclerosis is associated with cardiac rhabdomyomas.

Tuberous sclerosis is a neurocutaneous disorder that is inherited in an autosomal dominant fashion. Mutations in TSC1 and TSC2 lead to unregulated cell growth, leading to the formation of hamartomas in various locations. Manifestations of tuberous sclerosis include seizures (secondary to subependymal nodules and cortical dysplasia), mental retardation, renal angiomyolipomas, facial angiofibromas, mitral regurgitation, and hypomelanotic macules (ash-leaf spots). Cardiac rhabdomyoma is strongly associated with tuberous sclerosis and can lead to arrhythmias. West syndrome, which is characterized by infantile spasms, intellectual disability, and hypsarrhythmia (a chaotic mixture of high-amplitude slow waves, multifocal spikes, and intrahemispheric-interhemispheric asynchrony) on EEG, is also associated with tuberous sclerosis. Diagnosis of tuberous sclerosis is made with genetic testing. Advanced imaging (CT or MRI) may reveal cortical tubers and lesions in the third and fourth ventricles. Abdominal imaging may reveal renal angiomyolipomas. The management of seizures in tuberous sclerosis includes anti-seizure medications, though surgery may also be pursued in select cases.

Hinton et al. studied the cardiac manifestations of tuberous sclerosis. They found that cardiac rhabdomyomas can lead to arrhythmia later in life. They recommended that infantile spasms in tuberous sclerosis be treated with vigabatrin but other seizure types should be treated similar to other epileptic disorders.

Incorrect Answers:
Answer B: Glaucoma may occur in patients with Sturge-Weber syndrome, which is characterized by "tram-track" calcifications in the brain, port-wine stains of the face, mental retardation, and epilepsy. Diagnosis is with MRI of the brain with contrast to demonstrate leptomeningeal vascular malformations that are characteristic of the disease.

Answer C: Optic glioma is associated with neurofibromatosis type 1 (NF1), which presents with hyperpigmented macules (cafe-au-lait spots), axillary freckling, and cutaneous neurofibromas. Neurofibromas in NF1 may also grow on peripheral nerves, leading to malignant peripheral nerve sheath tumors. Lisch nodules, or benign growths of the iris, may also be seen in NF1. Diagnosis of NF1 is clinical, but can be aided by genetic testing.

Answer D: Polyostotic fibrous dysplasia is associated with McCune-Albright syndrome. Polyostotic fibrous dysplasia causes fibrous tissue in bones, leading to growth abnormalities and pathologic fractures. McCune-Albright syndrome is also associated with cafe-au-lait macules, which have irregular borders, and endocrine abnormalities such as precocious puberty and hyperthyroidism. Diagnosis is supported with endocrine tests as well as genetic testing.

Answer E: Renal cell carcinoma is associated with Von-Hippel-Lindau syndrome (VHL), which presents with tumors arising in multiple organs. Patients with VHL present with hemangioblastomas in the brain, spinal cord, cerebellum, and retina, and pheochromocytoma. Pheochromocytomas release catecholamines, leading to episodic hypertension, diaphoresis, and palpitations. Diagnosis of VHL is with genetic testing.

Bullet Summary:
Tuberous sclerosis has numerous manifestations including seizures, angiofibromas, mitral regurgitation, renal angiomyolipoma, ash-leaf spots, mental retardation, and cardiac rhabdomyoma.


Question: A 55-year-old man presents to urgent care for weakness and weight loss. For the past several months, he has felt progressively weaker and has lost 25 pounds with intermittent abdominal pain. The patient has not seen a physician in 30 years and recalls being current on most of his vaccinations. A few years ago, he went to the emergency department due to abdominal pain and was found to have increased liver enzymes due to excessive alcohol use and incidental gallstones. The patient has a 50 pack-year smoking history. His temperature is 99.5°F (37.5°C), blood pressure is 161/108 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 95% on room air. Physical exam reveals an emaciated man. The patient has a negative Murphy sign and his abdomen is non-tender. Cardiopulmonary exam is within normal limits. Which of the following is the most appropriate next step in management?

Smoking cessation advice and primary care follow up

Answer: CT scan of the abdomen and pelvis

Explanation:
This patient with weight loss and painless liver dysfunction has symptoms that are suggestive of pancreatic cancer. The most appropriate next diagnostic test is a CT scan of the abdomen and pelvis.

Pancreatic cancer presents with weight loss, jaundice, epigastric pain, and fatigue/malaise typically in an older male smoker who uses alcohol. Laboratory tests will demonstrate an elevated alkaline phosphatase and bilirubin. If a patient is presenting with the classic "painless jaundice" then the most appropriate next step in management could be an ultrasound to evaluate for obstruction. Otherwise, the best diagnostic test for this condition is a CT scan of the abdomen to characterize the pancreas and any metastasis to local organs. Treatment is with excision of the tumor through a Whipple procedure in appropriate candidates.

Lee and Lee review the evidence regarding the diagnosis of pancreatic cancer. They discuss how abdominal CT or MRI are important in making this diagnosis. They recommend having a high clinical index of suspicion given this diagnosis carries a high mortality rate.

Incorrect Answers:
Answer B: CT scan of the chest would be appropriate to screen a smoker for lung cancer. If this patient had concern for malignancy with a smoking history, then a CT scan of the chest would be appropriate. It would be appropriate at a later time to assess for pulmonary nodules and lung cancer.

Answer C: HIDA (hepatobiliary iminodiacetic acid) scan is an appropriate diagnostic test to characterize a gallstone blockage of the common bile duct if a right upper quadrant ultrasound is not revealing in the diagnosis of acute cholecystitis.

Answer D: A right upper quadrant ultrasound can assess the gallbladder for stones and the liver for an abscess, but it will not assess the pancreas for pancreatic cancer (at least in a reliable manner that assesses the entire pancreas).

Answer E: Smoking cessation and primary care follow up would be appropriate management for this patient if he only presented requesting general advice to improve his health or stop smoking. His current symptoms are too alarming for malignancy. He should stop smoking regardless.

Bullet Summary:
The most appropriate initial test for pancreatic cancer is an abdominal CT.


Question:
A 26-year-old woman presents to the emergency department with 1 day of vaginal bleeding and lower abdominal pain. The pain is most pronounced in the lower abdomen and has gotten worse over the past day. Her last menstrual period was 7 weeks ago. She denies any recent abdominal or vaginal trauma. She has no other past medical history and takes no medications. She uses a copper intrauterine device and is in a monogamous relationship. Her temperature is 99°F (37.2°C), blood pressure is 79/50 mmHg, pulse is 135/min, and respirations are 20/min. Physical examination is notable for diffuse abdominal tenderness upon palpation. Pelvic examination demonstrates uterine and adnexal tenderness and uterine bleeding. Laboratory studies are shown below:

Hemoglobin: 9.5 g/dL
Leukocyte count: 6,000/mm^3
Serum beta-human chorionic gonadotropin (hCG): 2,700 IU/L

The patient is started on intravenous fluids. Which of the following is the most appropriate next step in management?

Answer: Laparoscopy

Explanation:
This patient’s acute onset abdominal pain with uterine bleeding and tenderness, positive pregnancy test, anemia, and hemodynamic instability are concerning for a ruptured ectopic pregnancy. Emergency laparoscopy is the most appropriate next step in management.

An ectopic pregnancy, due to implantation of a fertilized ovum outside the uterine cavity, most commonly in the fallopian tube, can be life-threatening if it ruptures leading to intra-abdominal hemorrhage and shock. Initial laboratory studies should include a complete blood count and a pregnancy test. A patient’s hemodynamic stability should be ascertained immediately as it determines the most appropriate next step in management. In patients who are hemodynamically unstable (hypotensive and tachycardic), a Focused Assessment with Sonography for Trauma (FAST) exam should be immediately performed to evaluate for intraperitoneal bleeding, and ob/gyn should be immediately consulted for emergent surgical intervention (e.g., salpingectomy or salpingotomy). In patients who are hemodynamically stable, transvaginal ultrasound should be performed to determine the gestational sac location, and medical therapy can be initiated (e.g., methotrexate therapy, depending on the size and location of the pregnancy).

Cheng et al. compare fertility outcomes of salpingotomy and salpingectomy in women with tubal pregnancies. The authors found that there was no difference in intrauterine pregnancy rates or repeat ectopic pregnancy rates between patients that underwent salpingotomy or salpingectomy. The authors recommend that both salpingectomy and salpingotomy are reasonable options for the surgical management of tubal pregnancies.

Incorrect Answers:
Answer A: CT of the abdomen and pelvis is useful in determining if there is an intra-abdominal hemorrhage in patients who are hemodynamically stable. Unstable patients should generally not undergo CT.

Answer C: Methotrexate therapy is an effective treatment option in patients who are hemodynamically stable. with smaller ectopic pregnancies and lower hCG levels.

Answer D: Repeat beta-hCG in 48 hours is reserved for hemodynamically stable patients with non-diagnostic findings on transvaginal ultrasound. If the beta-hCG level is below the discriminatory zone (beta-hCG level 1,500-2,500 IU/L), then it should be repeated in 48 hours.

Answer E: Transvaginal ultrasound is reserved for hemodynamically stable patients who are presenting with abnormal uterine bleeding with abdominal/pelvic pain.

Bullet Summary:
Patients who present with a ruptured ectopic pregnancy with hemodynamic instability are managed with emergent surgical intervention.


Question: A 24-year-old man presents to his primary care physician with left groin pain. The pain started a year ago and has progressed. He now has 8/10 pain when climbing stairs or rising from a seated position. He localizes the pain to the front of his groin. He denies any erythema or swelling. He has a history of hypertension, sickle cell anemia, and a splenectomy. He drinks a glass of wine with dinner every night and took up scuba diving 2 months ago but otherwise does not exercise. His temperature is 97.5°F (36.4°C), blood pressure is 124/68 mmHg, pulse is 82/min, and respirations are 16/min. His body mass index (BMI) is 18.1 kg/m^2. Physical exam reveals left groin pain at the terminal ranges of hip abduction and internal rotation. There is no point tenderness. A radiograph is obtained as in Figure A. Which of the following components of this patient’s history most strongly predisposed him to this condition?

Answer: History of sickle cell disease

Explanation:
This patient with sickle cell disease (SCD) presents with anterior groin pain, especially with weight-bearing, and radiographic findings of amorphous lytic and sclerotic lesions of the femoral head, consistent with avascular necrosis. SCD is a predisposing factor for avascular necrosis.

Avascular necrosis has a multitude of direct causes, including irradiation, trauma (history of femoral neck fracture), hematologic diseases such as leukemia, SCD, and idiopathic etiology. In traumatic causes, injury to the medial femoral circumflex artery supplying the femoral head causes vascular disruption with resulting osteonecrosis. In SCD, the propensity for sickle-shaped erythrocytes to stick to one another and occlude blood vessels results in loss of circulation to the femoral head with consequent osteonecrosis. Avascular necrosis of the femoral head presents with insidious onset of anterior groin pain. The diagnosis can be secured with plain radiographs, although magnetic resonance imaging has the highest sensitivity and specificity for uncertain cases. Treatment consists of bisphosphonates with crutches (non-weight-bearing) and/or surgery depending on the degree of femoral head collapse and etiology.

Akinyoola et al. studied the risk factors associated with avascular necrosis of the femoral head in patients with sickle cell disease. The authors found that the rate of pain crises and annual hospitalizations are associated with avascular necrosis. The authors recommend further study to explain differences in the prevalence of osteonecrosis in different populations with sickle cell disease.

Figure/Illustration A shows a plain radiograph of the left hip in a skeletally mature individual, demonstrating amorphous cortical lesions (red arrows) in the femoral head and cortical irregularity (blue arrow) typical of avascular necrosis.

Incorrect Answers:
Answer A: Excess alcohol use has been associated with the risk of avascular necrosis. This patient uses alcohol in moderation (2 drinks or fewer per day for men) and has no history of alcohol use disorder.

Answer C: Lack of physical activity is a predisposing factor for osteoporosis but is not associated with avascular necrosis. Osteoporosis may increase the risk of a hip fracture, which would present with a painful, shortened, and externally rotated lower extremity.

Answer D: Low BMI is not a predisposing factor for avascular necrosis. In contrast, obesity has been associated with an increased risk of avascular necrosis.

Answer E: Scuba diving can indirectly predispose patients to avascular necrosis through decompression sickness (Caisson Disease). In decompression, dissolved gases in the arterial supply form gas emboli, leading to microvascular occlusion and dysbaric osteonecrosis. However, this patient’s symptoms have been present for 1 year whereas he only recently began scuba diving.

Bullet Summary:
Sickle cell disease is a predisposing factor for avascular necrosis of the femoral head, which presents as insidious anterior groin pain.


Question: A 30-year-old man is evaluated in the post-anesthesia care unit for neck pain. He underwent a laparoscopic appendectomy and was treated for post-operative nausea and vomiting with metoclopramide. Approximately 20 minutes after receiving the medication, he developed pain and stiffness in his neck and eventually was unable to move his neck. His temperature is 98.6°F (37.0°C), pulse is 90/min, blood pressure is 130/80 mmHg, respirations are 16/min, and oxygen saturation is 98% on room air. Examination reveals an uncomfortable appearing man. His neck is rotated to the right and is unable to return to midline. Examination of the patient is shown in Figure A. Which of the following is the most appropriate next step in management?

Answer: Diphenhydramine

Explanation:
This patient is suffering from a metoclopramide-induced acute dystonic reaction. Treatment of this complication includes IV diphenhydramine or benztropine.

Dystonic reactions are reversible extrapyramidal symptoms that may include involuntary spasms or sustained contractions of the face, neck, torso, pelvis, extremities, and larynx. Medications that block dopamine D2 receptors carry the greatest risk for development of a dystonic reaction, most notably including neuroleptics, antidepressants, and antiemetics. A family history of dystonia increases the risk of developing a reaction (there is likely an underlying genetic predisposition). Diagnosis is typically based on history and clinical presentation. Intravenous anticholinergic agents are the first-line treatment, and symptoms typically resolve rapidly (within 1 hour) after initiation of these agents.

Dressler et al. discuss the diagnosis and management of medication-induced acute movement disorders, notably dystonic reactions. These reactions are most commonly caused by dopamine-receptor blocking agents, including antipsychotics and antiemetics. Cranial, pharyngeal, and cervical muscles are typically affected within the first 4 days of initiating treatment.

Figure A shows a patient with dystonia and torticollis; note the posturing of the extremities as well as how the head is tilted to the patient's right side while the chin is directed up and towards the left.

Incorrect Answers:
Answer A: Intramuscular botulinum toxin injection may be appropriate for chronic torticollis or other forms of chronic dystonia. This patient has acute dystonia that is generally able to be easily reversed with intravenous diphenhydramine.

Answer C: Intravenous haloperidol, a D2 receptor antagonist would not be appropriate. This patient's condition is due to the dopamine antagonist action of metoclopramide and would therefore be worsened with haloperidol.

Answer D: Observation would not be appropriate. This patient is experiencing an acute dystonic reaction that is uncomfortable and potentially dangerous. Acute dystonia is not likely to self resolve in a reasonable amount of time.

Answer E: Intravenous ondansetron may be a more appropriate option to treat this patient's nausea given his reaction to metoclopramide. However, it will not reverse the acute dystonic reaction and is not the most appropriate first step.

Bullet Summary:
Acute dystonic reaction may occur with administration of medications that block dopamine receptors (such as metoclopramide), and can be treated with intravenous diphenhydramine.


Question:
A 48-year-old man presents to the emergency room with a 2-hour history of severe abdominal pain, nausea, and vomiting. He states that he has not passed gas or had a bowel movement in 4 days and his pain has worsened and become constant over the past 2 hours. His only medical history includes an appendectomy that he underwent as a child, and he takes no daily medications. His temperature is 38.5°C (101.3°F), blood pressure is 92/60 mmHg, pulse is 138/min, and respirations are 25/min. His pulse oximetry is 99% on room air.There are no cardiopulmonary abnormalities on auscultation. His abdomen is distended and tender in all quadrants, with guarding and rebound present. He also has increased bowel sounds throughout. Laboratory results are as follows:

Hemoglobin: 11 g/dL
Leukocyte count: 16,500/mm^3 with normal differential
Platelets: 250,000/mm^3

Serum:
Creatinine: 1.0 mg/dL
Glucose: 95 mg/dL
Lipase: 45 U/L
Total bilirubin: 0.8 mg/dL
Alkaline phosphatase: 74 U/L
Aspartate aminotransferase (AST, GOT): 32 U/L
Alanine aminotransferase (ALT, GPT): 45 U/L
Lactate: 7.0 mmol/L

Which of the following is the most appropriate next step in management?

CT angiography of the abdomen and pelvis

Supportive care, NPO, and intravenous fluids

Answer: Urgent surgical intervention

Explanation:
This patient with abdominal pain, vomiting, and obstipation is now hemodynamically unstable with fever, leukocytosis, rising lactate, and worsening pain. He most likely has a complicated small-bowel obstruction (SBO) and should undergo immediate surgical intervention.

SBO occurs when the normal progression of intraluminal contents in the intestines is interrupted, with most cases stemming from mechanical blockages. A history of abdominal surgery is a risk factor for SBO due to the formation of adhesions. Patients with SBO can typically be managed conservatively including nasogastric tube suction (if discomfort and active vomiting), bowel rest, and intravenous fluid resuscitation. However, patients with findings of a complicated SBO (changes in abdominal pain, fever, leukocytosis, guarding, and hemodynamic instability) require emergent surgical intervention. Delay in abdominal exploration may lead to necrosis, perforation, infection and a significant risk of mortality.

Bower et al. review small bowel obstruction. They note the need for operative intervention only in those who fail conservative management. They recommend nonoperative management for most cases of small bowel obstruction.

Incorrect Answers:
Answer A: Broad-spectrum antibiotics and serial abdominal radiographs alone would not be appropriate for this patient with a deteriorating clinical picture (hemodynamically unstable, worsening abdominal pain, fever, leukocytosis, high lactate). Antibiotics are not indicated in patients with uncomplicated SBO but may be useful in reducing infection risk in patients with complicated SBO. This patient should undergo emergent abdominal exploration in addition to receiving broad-spectrum antibiotics as it is possible he has already experienced bowel perforation.

Answer B: Computed tomography angiography (CTA) is useful in the diagnosis of acute mesenteric ischemia, which classically presents with abdominal pain out of proportion to exam (severe pain without much tenderness), vomiting, abdominal distention, and decreased bowel sounds. However, severe peritonitis and obstipation are more characteristic of SBO, and this patient is too hemodynamically unstable to undergo further imaging before proceeding to surgery.

Answers 3 & 4: Nasogastric tube placement with supportive care can be used to conservatively manage patients with uncomplicated SBO. This hemodynamically unstable patient has a fever, guarding, peritoneal signs, and newly worsened abdominal pain, indicative of a complicated SBO. He should be taken emergently to the operating room as the next step in management.

Bullet Summary:
Patients with intestinal obstruction who have a surgical abdomen or hemodynamic instability should undergo immediate surgical intervention.


Question: A 60-year-old woman presents to the emergency department with back pain after gardening. Her pain is 7/10 in severity, non-radiating, and not relieved by rest. She has never experienced this pain in the past and denies fever, night sweats, unintentional weight loss, and bowel or bladder incontinence. She has hypertension for which she takes hydrochlorothiazide and had a recent asthma flare requiring a prednisone taper. She does not drink alcohol or smoke. Her temperature is 98.6°F (37.0°C), blood pressure is 120/80 mmHg, pulse is 90/min, and respirations are 18/min. Physical exam reveals an uncomfortable middle-aged woman in no acute distress. There is no tenderness to palpation of the spinous processes. Flexion of the hip with the knee extended while the patient is supine does not elicit any pain, nor does forced dorsiflexion of the foot at terminal hip extension. She has 5/5 strength to hip flexion, extension, abduction, and adduction; knee flexion and extension; and ankle dorsiflexion and plantarflexion bilaterally. Bilateral patellar and Achilles reflexes are 2+. Serum laboratory results are as follows: Hemoglobin: 12.0 g/dL Creatinine: 1.1 mg/dL Ca2+: 10.6 mg/dL Which of the following is the most likely diagnosis?

Answer: Lumbosacral strain

Explanation:
This patient presents with acute low back pain after physical exertion without radicular signs (e.g., motor or sensory changes in a nerve root distribution) and a negative straight leg raise, which are most consistent with lumbosacral strain.

The evaluation of acute low back pain is focused on eliciting clinical history and signs that would indicate further work-up. In patients without significant trauma, the presence of signs of spinal cord compression (e.g., urinary retention, bowel incontinence, saddle anesthesia, focal neurologic deficits), history of or strong risk factors for cancer, signs of infection, or risk of vertebral compression fracture should prompt additional work-up with imaging such as radiographs or magnetic resonance imaging. If none of these findings are present (most patients with acute low back pain in the primary care setting), then conservative therapy for 4-6 weeks consisting of non-steroidal anti-inflammatory drugs with or without physical therapy is indicated.

Patel and Ogle review the management of acute low back pain in the primary care setting. They outline the Waddell signs, which indicate the presence of a functional (signs of excessive pain behavior) aspect of pain. The authors recommend surgical evaluation only in patients with worsening neurologic deficits or intractable pain resistant to conservative treatment.

Incorrect Answers:
Answer A: Herniated discs occurs when the nucleus pulposus herniates through a weakened part of the annulus fibrosus of an intervertebral disc, resulting in spinal nerve root compression. This causes radicular findings at the level of compression, including weakness in hip abduction and ankle dorsiflexion with L5 involvement and weakness in ankle plantarflexion and reduced Achilles reflex with S1 involvement, and radiation of pain into the ipsilateral lower extremity. The straight leg raise test would be positive, as it exacerbates the nerve root compression.

Answer C: Multiple myeloma presents with hypercalcemia, anemia, renal failure, and lytic bone lesions causing bone pain. This patient has no constitutional symptoms to suggest a malignant process and has a mild elevation in serum calcium, which is likely due to her thiazide diuretic. The clear association of her back pain with exertion makes lumbosacral strain more likely.

Answer D: Spondylolisthesis occurs when a vertebral body is forwardly subluxated relative to the adjacent vertebral body. This presents as back pain alleviated by rest. Since this can narrow the spinal canal, it may also present with neurogenic claudication, manifesting as buttock or leg pain with walking that can be alleviated by bending forward. This patient’s back pain is not alleviated by rest and is associated with exertion.

Answer E: Vertebral compression fractures can present as back pain in a patient with minor or no trauma. These patients have osteoporosis and other risk factors like advanced age or chronic corticosteroid use and would have point tenderness at the site of fracture. This patient does not have point tenderness or risk factors.

Bullet Summary:
Lumbosacral strain is a common cause of acute low back pain that presents after physical exertion with no radicular signs and a negative straight leg raise test.


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 75-year-old man presents to the emergency department with fatigue. He has had severe nausea, vomiting, and diarrhea for the past 3 days. Today, his wife noticed that he was confused. The patient has a history of coronary artery disease with a drug-eluting stent placed 1 year ago, obesity, hypertension, and dyslipidemia. He denies chest pain or dyspnea, but complains of diffuse abdominal pain. His temperature is 99.0°F (37.2°C), blood pressure is 100/60 mmHg, pulse is 105/min, and respirations are 22/min. Physical exam reveals a confused man with dry mucous membranes. His abdomen is diffusely tender to palpation. Laboratory studies are ordered and notable for the following:

Serum:
Na+: 147 mEq/L
Cl-: 112 mEq/L
K+: 3.5 mEq/L
HCO3-: 14 mEq/L
BUN: 80 mg/dL
Glucose: 100 mg/dL
Creatinine: 2.1 mg/dL
Troponin: 0.10 mcg/L (normal < 0.01 mcg/L)

An ECG is ordered and is pending. Which of the following is the most appropriate management of this patient's elevated troponin?

Obtain a urinalysis and creatine phosphokinase level

Answer: Ringer lactate bolus

Explanation:
This patient with likely gastroenteritis (given his nausea, vomiting, and diarrhea) is dehydrated, as indicated by his low blood pressure, tachycardia, dry mucous membranes, and prerenal kidney injury (elevated BUN and creatinine with BUN:creatinine ratio > 20:1) in the setting of an anion gap (anion gap = [Na+] - [Cl-] - [HCO3-] = 147 - 112 - 14 = 21). His elevated troponin is likely secondary to poor renal clearance and dehydration, which is most appropriately addressed with IV fluids such as Ringer lactate.

Troponin is a lab marker classically thought to be elevated when there is an injury to the heart causing leakage of this enzyme from the cardiac myocyte. However, there are many possible causes of an elevated troponin that may not be directly cardiac in nature or related to myocardial ischemia. Acute kidney injury is a common cause of an elevated troponin. For this reason, patients with an elevated troponin with kidney dysfunction without any cardiac symptoms or ECG changes should have their renal etiology addressed, and this will often clear the troponin. In the setting of a prerenal injury (dehydration causing poor kidney perfusion and a BUN:creatinine ratio > 20:1), IV fluids will restore perfusion and treat the underlying cause. Patients with chronic kidney disease or kidney failure should have an ECG obtained and their current troponin should be compared to previous troponin levels to ensure it is not higher than their baseline. If there is uncertainty regarding a troponin level, it can be trended to see if it is rising, falling, or staying the same. Correlation with clinical symptoms is important when evaluating an elevated troponin level.

Masri et al. review the causes of an elevated troponin. They note that a troponin elevation can be seen in myopericarditis, renal failure, heart failure, pulmonary embolism, septic shock, rhabdomyolysis, stroke, and many other possible causes that are not related to myocardial infarction. They recommend keeping a broad differential and correlating the troponin with the patient's clinical presentation.

Incorrect Answers:
Answer A: Aspirin would be appropriate management of an elevated troponin secondary to acute coronary syndrome as its antiplatelet activity reduces mortality. It should be administered prior to performing an ECG in patients with chest pain thought to be from a cardiac etiology.

Answer B: Aspirin, heparin, clopidogrel, and cardiac catheterization is appropriate management of a ST elevation myocardial infarction, which presents with chest pain, diaphoresis, dyspnea, and ST elevation within a vascular distribution with reciprocal changes on ECG. This patient has no cardiac symptoms and has a better alternative explanation for their troponin elevation.

Answer C: Metoprolol and aspirin may be indicated in acute coronary syndrome, and metoprolol would reduce this patient's heart rate. However, note that this patient's tachycardia is secondary to volume depletion; thus, beta-blockade for sinus tachycardia is inappropriate and may make the patient hemodynamically unstable.

Answer D: Obtaining a urinalysis and creatine phosphokinase level may be performed in rhabdomyolysis which presents in the setting of seizures, electrical shock, heatstroke, or with vigorous exertion. Patients will complain of muscle pain, oliguria, and dark urine. Management is centered on the administration of large volumes of fluid to protect the kidney and clear the toxic myoglobin. Note that rhabdomyolysis may elevate the troponin; however, there is nothing in this patient's history that suggests rhabdomyolysis.

Bullet Summary:
Prerenal injury causing an acute kidney injury may elevate the troponin due to decreased renal clearance and should be addressed with the administration of fluids.


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 41-year-old man presents to his primary care provider with a 2-month history of abdominal pain. He says that the pain “comes and goes” throughout the day and usually lasts 20-30 minutes per episode. The pain is above his umbilicus. He denies any feeling of regurgitation or nighttime cough but endorses nausea. He used to eat 3 large meals per day but has found that eating smaller meals more frequently improves his pain. He tried ibuprofen with food and thinks it helped. He has gained 4 pounds since his last appointment 3 months ago. He denies any diarrhea or change in his stools. He has no known medical history. He drinks 5-6 beers on the weekend and has a 20 pack-year smoking history. He denies any family history of cancer. His temperature is 98.6°F (37°C), blood pressure is 117/72 mmHg, pulse is 72/min, and respirations are 13/min. On physical exam, he is tender to palpation above the umbilicus. Bowel sounds are present. A stool guaiac test is positive. The patient undergoes an endoscopy with a biopsy to diagnose his condition. Which of the following is most likely to be found on histology?

Noncaseating granulomas in the small intestine

PAS-positive material in the small intestine

Urease-producing organism in the small intestine

Answer: Urease-producing organism in the small intestine

Explanation:
This patient presents with episodic epigastric pain and nausea that improves with the consumption of food, which suggests a diagnosis of a duodenal ulcer. Duodenal ulcers are often caused by infection with Helicobacter pylori, a urease-producing organism.

Duodenal ulcers are erosions and defects in the mucosal lining of the small intestines that allow for damage to the underlying tissues. Patients will classically present with abdominal pain that is localized to the epigastric region. Duodenal ulcers improve upon eating due to the secretion of bicarbonate in the small intestines, whereas gastric ulcers are exacerbated by food due to the release of gastric acid in the stomach. Duodenal ulcers are most commonly caused by infection with H. pylori. If the patient tests positive for H. pylori infection, treatment involves triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor. Patients who fail to improve should undergo esophagogastroduodenoscopy, which remains the gold standard for diagnosis.

Ciociola et al. studied the prevalence of H. pylori infection in patients with gastric ulcers. They found that about many had confirmed infections. They recommend against empiric treatment without prior confirmation of infection.

Incorrect Answers:
Answer A: Crypt abscesses are found on histology in ulcerative colitis. Ulcerative colitis presents with bloody diarrhea and abdominal pain. Patients can also experience musculoskeletal pain, uveitis, and dermatologic findings such as erythema nodosum or pyoderma gangrenosum. Treatment may include mesalazine.

Answer B: A mucosal defect in the stomach is the pathologic description of a gastric ulcer. This patient’s presentation of epigastric pain that improves with the consumption of food is more consistent with an ulcer in the duodenum. Treatment of a gastric ulcer may include proton pump inhibitors.

Answer C: Noncaseating granulomas are found on histology in Crohn disease. This patient denies any diarrhea (often associated with pain), which is the primary feature of Crohn disease. Other findings include abscesses, fistulas, and strictures. Treatment may include mesalamine and infliximab.

Answer D: PAS-positive material is found in the lamina propria on small intestinal biopsy in Whipple disease. In addition to abdominal pain, Whipple disease is characterized by diarrhea with flatulence and steatorrhea, fever, arthralgias, and weight loss. Treatment is with ceftriaxone or penicillin.

Bullet Summary:
Duodenal ulcers typically present with episodic epigastric abdominal that is improved after eating and are associated with H. pylori infection.


Question: A 62-year-old man arrives at the emergency room complaining of chest pain and difficulty breathing. He reports that the dyspnea started 2 months ago after he had the flu. At first, the difficulty breathing occurred whenever he went up and down 1 flight of stairs, but the dyspnea progressively worsened since then. This morning, he developed chest pain and difficulty breathing while sitting at the kitchen table. The patient’s medical history is significant for hypertension, type 2 diabetes mellitus, and rheumatoid arthritis. His medications include aspirin, lisinopril, metformin, and sulfasalazine. His temperature is 97°F (36.1°C), blood pressure is 130/78 mmHg, pulse is 88/min, and respirations are 14/min with an oxygen saturation of 97% O2 on room air. On physical exam, jugular venous distension during both inspiration and expiration, mild abdominal distention, and 2+ bilateral lower extremity edema is noted. A chest radiograph is obtained and the result is shown in Figure A. Which of the following is the most likely cause of this patient's symptoms?

Answer: Constrictive pericarditis

Explanation:
This patient is presenting with peripheral edema, ascites, elevated jugular venous distension, and pericardial calcifications on chest radiograph, which are all consistent with a diagnosis of constrictive pericarditis.

Constrictive pericarditis is the result of scarring and loss of elasticity of the pericardial sac. Common etiologies include idiopathic, post-viral, post-cardiac surgery, post-radiation, tuberculosis-related, or connective tissue disorder-related. It presents as right heart failure including symptoms such as dyspnea, chest pain relieved by leaning forward, progressive peripheral edema, and ascites. A physical exam will identify an early diastolic pericardial knock, pericardial calcifications on chest radiograph, and jugular venous distension (JVD). Kussmaul sign can also occur where the JVD paradoxically rises during inspiration instead of falling. The diagnosis is supported with echocardiography. Management may require pericardiectomy for severe cases.

Welch and Oh review the evidence regarding the diagnosis and treatment of constrictive pericarditis. They discuss how this disease can be evaluated using a cardiac MRI. They recommend surgical pericardiectomy in many cases.

Figure/Illustration A is a frontal chest radiograph with pericardial calcifications (red circle). These findings are consistent with constrictive pericarditis.

Incorrect Answers:
Answer A: Cardiac tamponade can present similarly to constrictive pericarditis. Hypotension and pulsus paradoxus (a greater than 10 mmHg decrease in the systolic blood pressure during inspiration), will commonly present in patients with cardiac tamponade. A chest radiograph will show an enlarged cardiac silhouette rather than calcifications in some cases. Treatment is with emergent pericardial decompression.

Answer B: Cirrhosis can present with ascites and peripheral edema, but will not have a marked elevation in jugular venous pressure. Cirrhosis is the end-stage result of many hepatic pathologies. Treatment is with the control of sequelae such as hepatic encephalopathy and venous congestion.

Answer D: Pulmonary arterial hypertension, like constrictive pericarditis, can present with exertional dyspnea, chest pain, and peripheral edema if it progresses to right ventricular failure. A chest radiograph may show enlarged central pulmonary arteries and peripheral pulmonary vessels. Treatment is with reduction of pulmonary pressure such as with endothelin inhibitors.

Answer E: Restrictive cardiomyopathy can also present as right heart failure with similar symptoms to constrictive pericarditis. A history of an infiltrative disease (e.g., amyloidosis and sarcoidosis) often favors restrictive cardiomyopathy, as does an audible S3 on a physical exam. Calcification of the pericardium on the chest radiograph is more consistent with constrictive pericarditis.

Bullet Summary:
Constrictive pericarditis presents with symptoms of right heart failure, progressive peripheral edema, ascites, jugular venous distension, pericardial knock, and pericardial calcifications on a chest radiograph.


Question:
A 25-year-old woman presents to her primary care physician with joint and muscle pain. She has a general aching/pain in her joints that lasts all day. The pain is constant and is not relieved by rest or activity. She also has pain in her hands at times and occasionally notices trouble swallowing when she is eating. She has a medical history of anxiety and is not currently taking any medications. Her temperature is 98.6°F (37°C), blood pressure is 115/72 mmHg, pulse is 74/min, and respirations are 11/min. On physical exam, the patient is a healthy young woman with a sunburn. Her hands are mildly edematous with the findings in Figure A. Laboratory values are below:

Serum:
Na+: 145 mEq/L
K+: 4.4 mEq/L
Cl-: 100 mEq/L
HCO3-: 24 mEq/L
BUN: 9 mg/dL
Glucose: 70 mg/dL
Creatinine: .7 mg/dL
Ca2+: 10 mg/dL
Mg2+: 1.8 mEq/L

Which of the following antibodies is most likely to aid in making the diagnosis in this patient?

Answer: Anti-ribonuleoprotein

Explanation:
This patient is presenting with diffuse muscle/joint pain, Raynaud phenomenon, and dysphagia suggesting a diagnosis of mixed connective tissue disease. Anti-ribonucleoprotein (U1) antibodies are found in this disease.

Mixed connective tissue disease can present with a vast array of symptoms. The most common symptoms are Raynaud phenomenon (vascular hyper-reactivity that presents with burning/pain in the hands where the hands change color from white to blue to red, seen in Figure A), arthralgias, myalgias, dysphagia, and edema of the hands. Anti-U1 ribonucleoprotein antibodies are commonly found in mixed connective tissue disease and are a specific marker. In this disease, there is typically an absence of renal involvement. Treatment involves steroids as well as calcium channel blockers for symptomatic control of Raynaud phenomenon.

Batu et al. review the evidence regarding patients with mixed connective tissue disease. They found that many patients have overlapping symptoms with systemic lupus erythematosus and systemic sclerosis. They recommend studying patients with these mixed characteristics in order to better understand which treatment modalities are effective.

Figure/Illustration A is a clinical photograph showing the blanching of the distal fingers (red box). This finding demonstrates the Raynaud phenomenon during the early phase where the vessels have spasmed.

Incorrect Answers:
Answer A: Anti-dsDNA is a specific marker in systemic lupus erythematosus (SLE). SLE presents with SOAP BRAIN MD - Serositis, Oral ulcers, Arthritis, Photosensitivity, Blood disorders (hemolytic anemia, etc.), Renal involvement, ANA, Immune phenomena (anti-dsDNA, Smith), Neurological symptoms, Malar rash, and Discoid rash. Four of these criteria must be met to suspect a diagnosis of SLE. Treatment is with hydroxychloroquine.

Answer B: Anti-IgG Fc region is representative of rheumatoid factor which is found in rheumatoid arthritis. Rheumatoid arthritis can present with fever, weight loss, and joint pain that worsens in the morning and improves with activity. It is common for the joints of the hands to become deformed due to the disease process. Treatment is with methotrexate.

Answer C: Anti-nuclear antibodies (ANA) are likely positive in this patient; however, they are not more likely to aid in making the diagnosis than anti-ribonucleoprotein antibodies are. ANA are non-specific and can be found in many rheumatological conditions such as MCTD, lupus, and rheumatoid arthritis.

Answer E: Anti-Ro antibodies are found in Sjogren syndrome which presents with dry eyes, dry mouth, dental caries, and dyspareunia. A salivary gland biopsy can be used to confirm the diagnosis. Treatment includes artificial tears, vitamin D supplementation, and pilocarpine or cevimeline.

Bullet Summary:
Mixed connective tissue disease is associated with anti-ribonuleoprotein antibodies and presents with Raynaud phenomenon, arthralgia/arthritis, swollen hands, sclerodactyly, and myositis.


Question: A 32-year-old man presents to the emergency department for evaluation of headache. His symptoms started last night and have persisted. He occasionally has migraine headaches, but he has not had a headache like this in the past. He reports associated nausea, vomiting, fevers, and neck pain. He has a medical history of asthma. His temperature is 100.4°F (38.0°C), blood pressure is 110/60 mmHg, pulse is 95/min, respirations are 17/min, and oxygen saturation is 98% on room air. On physical exam, he appears uncomfortable. Neurologic exam reveals no focal deficits. There is pain with passive neck flexion. No edema or rashes are noted. Lungs are clear to auscultation bilaterally. Lumbar puncture is performed and CSF results are obtained as shown below. Cerebrospinal fluid (CSF): Cell count: 175/mm^3 RBCs: 0/mm^3 Cl-: 119 mEq/L Glucose: 49 mg/dL Pressure: 150 mmH2O Total protein: 55 mg/dL Based on these results, which of the following is the most appropriate treatment regimen for this patient?

Answer: Supportive care and monitoring

Explanation:
This patient with headache, fever, and neck stiffness has a presentation and CSF studies consistent with a diagnosis of viral or aseptic meningitis. Supportive care is the most appropriate management strategy for patients with viral meningitis.

Aseptic (viral) meningitis presents similarly to bacterial meningitis with neck stiffness, photophobia, fever, malaise, and flu-like symptoms. Patients should be worked up and treated as if they have bacterial meningitis until proven otherwise. CSF findings in aseptic meningitis show an elevated cell count (though typically < 300/mm^3 in contrast to bacterial meningitis), a normal or elevated protein, and a normal glucose. CSF should be sent for Gram stain and culture to confirm the diagnosis and rule out bacterial meningitis. Once the diagnosis has been confirmed, management of viral meningitis consists of supportive care and monitoring for complications such as seizures, cerebral edema, or SIADH.

Kohil et. al review viral meningitis. They discuss the pathophysiology, clinical manifestation and diagnosis. They recommend that most patients with viral meningitis be treated with supportive care.

Incorrect Answers:
Answer A: Acyclovir would be appropriate for suspected HSV or varicella encephalitis or meningitis. This patient with no RBCs in the CSF and no changes in mental status is not likely to have infection with HSV or varicella.

Answer B: Amphotericin and 5-flucytosine followed by long-term fluconazole is the appropriate management of cryptococcal meningitis. Cryptococcal meningitis presents similarly to bacterial and viral meningitis, almost exclusively in immunocompromised patients.

Answer C: Ceftriaxone and vancomycin would be appropriate if bacterial meningitis was suspected. Steroids are generally added if a bacterial source is likely. However, this patient has a presentation that is less concerning for bacterial meningitis, and CSF studies that are more consistent with aseptic meningitis.

Answer D: Ceftriaxone, vancomycin and steroids are an appropriate initial regimen for bacterial meningitis. Dexamethasone reduces inflammatory injury while patients are being treated with antibiotics.

Bullet Summary:
Viral or aseptic meningitis is managed with supportive care and monitoring.


Question: A 44-year-old man presents to the emergency department with palpitations. He has a history of anxiety managed with fluoxetine and lorazepam. He also has hypertension but does not take any medications. Today, his symptoms have been persistent despite taking his medications. He says that he feels lightheaded and can’t walk. His temperature is 98.7°F (37.1°C), blood pressure is 120/72 mmHg, pulse is 183/min, respirations are 25/min, and oxygen saturation is 99% on room air. Physical exam reveals a somnolent and uncomfortable man. His pulse is rapid and regular. An ECG is performed as seen in Figure A. During the exam, the patient states that he feels lightheaded and appears occasionally somnolent. Which of the following is the most appropriate treatment for this patient?

Answer: Cardioversion

Explanation:
This patient is presenting with palpitations and an ECG demonstrating a wide complex tachycardia with a delta wave which are concerning for a tachydysrhythmia secondary to Wolff Parkinson White syndrome. Given his poor CNS perfusion (somnolence during his tachycardia despite a “normal” blood pressure), the most appropriate next step in management is cardioversion.

Wolff Parkinson White syndrome (WPW) is a pre-excitation syndrome where an accessory electrical pathway exists between the atria and ventricles that bypasses the AV node. WPW can demonstrate antidromic conduction where the accessory pathway leads to anterograde conduction causing a wide-complex tachycardia that is often mistaken for ventricular tachycardia. In this circumstance, the QRS is wide and a delta wave is often present but may be difficult to discern. If ever uncertain as to whether the diagnosis is ventricular tachycardia or WPW, cardioversion is a safe and effective intervention for both rhythms. Unstable patients with either WPW or ventricular tachycardia should undergo cardioversion immediately. Other treatments for WPW in stable patients may include procainamide. Ablation may present future episodes.

Bartlett and Friedman review the pathophysiology of WPW. They discuss the congenital presence of impulse-conducting fascicles leading to this condition. They also delve into the management and recommend rhythm agents and ablation as a modality of treatment.

Figure/Illustration A is an ECG demonstrating a wide complex (red arrow) tachycardia with a delta wave (blue arrow). These ECG findings are characteristically seen in WPW syndrome.

Incorrect Answers:
Answer A: Adenosine would be indicated after vagal maneuvers in the management of supraventricular tachycardia (SVT). SVT presents as a narrow complex tachycardia without P waves. It is regular (in contrast to atrial fibrillation). Failure to respond to vagal maneuvers or adenosine warrants cardioversion. If this patient was perfusing his CNS, a trial of adenosine could be appropriate given it has a short half-life and may differentiate ventricular tachycardia from SVT with aberrancy or a bundle branch block.

Answer B: Amiodarone may be used in stable ventricular tachycardia to control the rhythm and convert it to sinus. It would not be appropriate in a hemodynamically unstable patient. It can be used in other dysrhythmias as well including atrial fibrillation and atrial flutter.

Answer D: Defibrillation is only indicated in pulseless, shockable rhythms including ventricular fibrillation (disorganized electrical activity), pulseless ventricular tachycardia (wide complex tachycardia), and pulseless torsades des pointes (twisting of the QRS complexes around an isoelectric baseline). It could cause cardiac arrest if performed on a patient with a pulse.

Answer E: Procainamide is an antidysrhythmic that can be used in tachydysrhythmias that occur in WPW. Given that this patient is unstable, it is more appropriate to perform cardioversion.

Bullet Summary:
Unstable tachyarrhythmias in the setting of Wolff Parkinson White syndrome require cardioversion.


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 16-year-old girl who recently immigrated to the United States from Bolivia presents to her primary care physician with a chief complaint of inattentiveness in school. The patient's teacher describes her as occasionally "daydreaming" for periods of time during where the patient does not respond or participate in school activities. Nothing has helped the patient change her behavior, including parent-teacher conferences or punishment. The patient has no other concerns. The only other concern that the patient's mother has is that, upon awakening, she notices that sometimes the patient's arm will jerk back and forth. The patient states she is not doing this intentionally. The patient has an unknown medical history and is currently not on any medications. She is not sexually active and does not intend to become pregnant in the near future. Her temperature is 98.6°F (37°C), blood pressure is 112/74 mmHg, pulse is 63/min, and respirations are 11/min. On physical exam, you note a young, healthy girl whose neurological exam is within normal limits. Which of the following is the most appropriate initial treatment?

Answer: Valproic acid

Explanation:
This patient is presenting with both absence seizures (periods of inattentiveness in school) and juvenile myoclonic epilepsy (abnormal, involuntary spasms of her upper extremity). The most appropriate treatment for these conditions is valproic acid.

Absence seizures classically present with cessation of motor activity and speech with a blank facial expression and occasionally automatisms such as flickering of the eyelids. They can be mistaken for inattentiveness in school-aged children. Juvenile myoclonic epilepsy presents with a "jerky" movement of the patient's extremity that typically occurs in the morning and begins around adolescence. The only medication that can be used to treat both absence seizures and juvenile myoclonic epilepsy is valproic acid. Valproic acid inhibits GABA transaminase, blocks thalamic T-type calcium channels, and blocks voltage-gated sodium channels. In post-pubertal female patients, it is important to counsel them on the potential teratogenic effects of this medication and also to consider alternative treatments in patients who are considering becoming pregnant or who cannot guarantee reliable birth control practices.

Kessler and McGinnis discuss the treatment of childhood absence seizures. They discuss how the treatment of choice is ethosuximide due to its favorable side effect profile. They recommend using valproic acid if there are concurrent seizure conditions.

Incorrect Answers:
Answer A: Carbamazepine would be the appropriate therapy for a partial seizure (tonic or clonic movements in addition to an absence of a post-ictal period) or for trigeminal neuralgia (sudden pain in the distribution of the trigeminal nerve). It would not address both absence seizures and juvenile myoclonic epilepsy.

Answer B: Cognitive behavioral therapy is a useful treatment that helps a patient develop coping strategies and change unhelpful patterns of thought. It could be useful if this girl was having trouble focusing in school for another reason (such as obsessive-compulsive disorder); however, it is not useful in managing seizures.

Answer C: Ethosuximide is the most appropriate initial therapy for absence seizures. In this patient, she is suffering from both absence seizures and juvenile myoclonic epilepsy which could not be treated by ethosuximide alone, in contrast to valproic acid which could treat both conditions.

Answer D: Lamotrigine is an anti-epileptic that can also be used as a mood stabilizer. It carries the potentially severe side effect of Stevens-Johnson syndrome. It is not a first-line treatment for absence seizures and juvenile myoclonic epilepsy. Stevens-Johnson syndrome will present with painful desquamation.

Bullet Summary:
Absence seizures present with periods of inattentiveness and subtle automatisms and are most appropriately treated with ethosuximide or with valproic acid if there is concurrent juvenile myoclonic epilepsy.