A 21-year-old woman presents with right eye irritation, redness, and watery discharge. These symptoms started abruptly 4 days ago. She is on summer vacation and does not report any contacts with evidently ill patients. However, during the vacation, she frequently visited crowded places. The patient denies any other symptoms. At the presentation, the patient's vital signs include: blood pressure 125/80 mm Hg, heart rate 75/min, respiratory rate 14/min, and temperature 36.7℃ (98℉). The physical examination shows conjunctival injection, watery discharge, and mild follicular transformation of the conjunctiva of the right eye. There are no corneal lesions. Ipsilateral preauricular lymph nodes are enlarged. Which of the following would be a proper medical therapy for this patient?
Q52
A 68-year-old man is brought to the emergency department 25 minutes after he was found shaking violently on the bathroom floor. His wife reports that he has become increasingly confused over the past 2 days and that he has been sleeping more than usual. He was started on chemotherapy 4 months ago for chronic lymphocytic leukemia. He is confused and oriented to person only. Neurological examination shows right-sided ptosis and diffuse hyperreflexia. An MRI of the brain shows disseminated, nonenhancing white matter lesions with no mass effect. A polymerase chain reaction assay of the cerebrospinal fluid confirms infection with a virus that has double-stranded, circular DNA. An antineoplastic drug with which of the following mechanisms of action is most likely responsible for this patient's current condition?
Q53
A 24-year-old man presents with difficulty breathing and blurred vision in the left eye. No significant past medical history or current medications. He has had more than 6 sexual partners (both men and women) and did not use any form of protection during sexual intercourse. No significant family history. Upon physical examination, the patient has crackles in all lobes bilaterally. Ophthalmologic exam reveals a single white lesion in the left eye with an irregular, feathery border, as well as evidence of retinal edema and necrosis. A rapid HIV test is positive. What is the mechanism of action of the drug that can be given to treat the ocular symptoms in this patient?
Q54
A public health researcher is invited to participate in a government meeting on immunization policies. Other participants in the meeting include physicians, pediatricians, representatives of vaccine manufacturers, persons from the health ministry, etc. For a specific viral disease, there are 2 vaccines - one is a live attenuated vaccine (LAV) and the other is a subunit vaccine. Manufacturers of both the vaccines promote their own vaccines in the meeting. Non-medical people in the meeting ask the public health researcher to compare the 2 types of vaccines objectively. The public health researcher clearly explains the pros and cons of the 2 types of vaccines. Which of the following statements is most likely to have been made by the public health researcher in his presentation?
Q55
A 39-year-old man comes to the physician because of a 4-month history of fatigue. During this period, he has also had a 7.7-kg (17-lb) weight loss, despite having a normal appetite. He is sexually active with 3 female partners and uses condoms inconsistently. An HIV screening test and confirmatory test are both positive. CD4+ T-lymphocyte count is 570/mm3 (N ≥ 500) and the viral load is 104 copies/mL. Treatment with lamivudine, zidovudine, and indinavir is begun. The patient is most likely to experience which of the following adverse effects?
Q56
A 17-year-old girl presents to the emergency department with a severe headache. The patient has had headaches in the past, but she describes this as the worst headache of her life. Her symptoms started yesterday and have been getting progressively worse. The patient states that the pain is mostly on one side of her head. There has been a recent outbreak of measles at the patient’s school, and the patient’s mother has been trying to give her daughter medicine to prevent her from getting sick, but the mother fears that her daughter may have caught the measles. On physical exam, you note an obese young girl who is clutching her head with the light in the room turned off. Her neurological exam is within normal limits. Fundoscopic exam reveals mild bilateral papilledema. A MRI of the head is obtained and reveals cerebral edema. A lumbar puncture reveals an increased opening pressure with a normal glucose level. Which of the following is the most likely diagnosis?
Q57
A 61-year-old woman presents to her primary care physician complaining of left-sided facial pain that started yesterday. She describes the pain as stinging, burning, and constant. It does not worsen with jaw movement or chewing. Her past medical history includes hyperlipidemia and multiple sclerosis (MS), and she had chickenpox as a child but received a shingles vaccination last year. Medications include simvastatin and glatiramer acetate. The patient’s last MS flare was 5 weeks ago, at which time she received a prednisone burst with taper. At this visit, her temperature is 99.9 °F (37.7°C), blood pressure is 139/87 mmHg, pulse is 82/min, and respirations are 14/min. On exam, there is no rash or skin change on either side of the patient’s face. Gentle palpation of the left cheek and mandible produce significant pain, but there is full range of motion in the jaw. Which of the following medications is the most likely to prevent long-term persistence of this patient’s pain?
Q58
A 67-year-old man presents to the emergency department with confusion. The patient is generally healthy, but his wife noticed him becoming progressively more confused as the day went on. The patient is not currently taking any medications and has no recent falls or trauma. His temperature is 102°F (38.9°C), blood pressure is 126/64 mmHg, pulse is 120/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam is notable for a confused man who cannot participate in a neurological exam secondary to his confusion. No symptoms are elicited with flexion of the neck and jolt accentuation of headache is negative. Initial laboratory values are unremarkable and the patient's chest radiograph and urinalysis are within normal limits. An initial CT scan of the head is unremarkable. Which of the following is the best next step in management?
Q59
A 22-year-old man comes to the physician for a follow-up evaluation for chronic lower back pain. He has back stiffness that lasts all morning and slowly improves throughout the day. He has tried multiple over-the-counter medications, including ibuprofen, without any improvement in his symptoms. Physical examination shows tenderness over the iliac crest bilaterally and limited range of motion of the lumbar spine with forward flexion. The results of HLA-B27 testing are positive. An x-ray of the lumbar spine shows fusion of the lumbar vertebrae and sacroiliac joints. The physician plans to prescribe a new medication but first orders a tuberculin skin test to assess for the risk of latent tuberculosis reactivation. Inhibition of which of the following is the most likely primary mechanism of action of this drug?
Q60
A 26-year-old man comes to the physician for a follow-up examination. He was diagnosed with HIV infection 2 weeks ago. His CD4+ T-lymphocyte count is 162/mm3 (N ≥ 500). An interferon-gamma release assay is negative. Prophylactic treatment against which of the following pathogens is most appropriate at this time?
Antivirals US Medical PG Practice Questions and MCQs
Question 51: A 21-year-old woman presents with right eye irritation, redness, and watery discharge. These symptoms started abruptly 4 days ago. She is on summer vacation and does not report any contacts with evidently ill patients. However, during the vacation, she frequently visited crowded places. The patient denies any other symptoms. At the presentation, the patient's vital signs include: blood pressure 125/80 mm Hg, heart rate 75/min, respiratory rate 14/min, and temperature 36.7℃ (98℉). The physical examination shows conjunctival injection, watery discharge, and mild follicular transformation of the conjunctiva of the right eye. There are no corneal lesions. Ipsilateral preauricular lymph nodes are enlarged. Which of the following would be a proper medical therapy for this patient?
A. Acyclovir ointment
B. Oral erythromycin
C. No medical treatment required (Correct Answer)
D. Levofloxacin drops
E. Tetracycline ointment
Explanation: ***No medical treatment required***
- The patient's symptoms (right eye irritation, redness, watery discharge, follicular conjunctivitis, enlarged preauricular lymph nodes) are characteristic of **viral conjunctivitis**, which is typically **self-limiting**.
- Treatment is primarily **supportive**, focusing on comfort measures like cool compresses, as antiviral medications are usually not indicated unless there's evidence of herpes simplex keratitis, which is not present here.
*Acyclovir ointment*
- **Acyclovir ointment** is an antiviral medication used to treat **herpes simplex keratitis** or conjunctivitis.
- The patient's presentation of **watery discharge** and **follicular conjunctivitis** is more consistent with adenovirus, but there are **no corneal lesions** or other features suggestive of herpes simplex virus.
*Oral erythromycin*
- **Oral erythromycin** is an antibiotic used for systemic bacterial infections or for chlamydial conjunctivitis in neonates.
- It is **not indicated** for viral conjunctivitis, and there is no evidence of a bacterial infection in this case, given the watery discharge and lack of purulence.
*Levofloxacin drops*
- **Levofloxacin drops** are a topical antibiotic used to treat **bacterial conjunctivitis**.
- The patient's **watery discharge**, follicular reaction, and enlarged preauricular lymph nodes are classic signs of **viral conjunctivitis**, which does not respond to antibiotics.
*Tetracycline ointment*
- **Tetracycline ointment** is an antibiotic primarily used for bacterial conjunctivitis, particularly for **Chlamydia trachomatis** infections.
- The clinical presentation with watery discharge and follicular conjunctivitis, in this context, is more suggestive of a viral etiology than bacterial or chlamydial, making antibiotics inappropriate.
Question 52: A 68-year-old man is brought to the emergency department 25 minutes after he was found shaking violently on the bathroom floor. His wife reports that he has become increasingly confused over the past 2 days and that he has been sleeping more than usual. He was started on chemotherapy 4 months ago for chronic lymphocytic leukemia. He is confused and oriented to person only. Neurological examination shows right-sided ptosis and diffuse hyperreflexia. An MRI of the brain shows disseminated, nonenhancing white matter lesions with no mass effect. A polymerase chain reaction assay of the cerebrospinal fluid confirms infection with a virus that has double-stranded, circular DNA. An antineoplastic drug with which of the following mechanisms of action is most likely responsible for this patient's current condition?
A. Monoclonal antibody against CD20+ (Correct Answer)
B. Monoclonal antibody against EGFR
C. Tyrosine kinase inhibitor
D. Topoisomerase II inhibitor
E. Free radical formation
Explanation: **Monoclonal antibody against CD20+**
- The patient's presentation with **progressive multifocal leukoencephalopathy (PML)**, characterized by neurological deficits, white matter lesions, and a positive PCR for a **double-stranded, circular DNA virus (JC virus)**, strongly suggests a compromised immune system, likely due to chronic lymphocytic leukemia (CLL) treatment.
- **Rituximab**, a monoclonal antibody that targets **CD20+ B-lymphocytes**, is a common treatment for CLL and is associated with an increased risk of PML due to its immunosuppressive effects.
*Monoclonal antibody against EGFR*
- **Epidermal growth factor receptor (EGFR) inhibitors** (e.g., cetuximab, erlotinib) are used in various cancers but are not typically associated with the development of PML.
- Side effects of EGFR inhibitors commonly include skin rashes, diarrhea, and stomatitis, not the neurological symptoms seen here.
*Tyrosine kinase inhibitor*
- **Tyrosine kinase inhibitors (TKIs)**, such as imatinib or ibrutinib, are used in certain leukemias and other cancers.
- While TKIs can have various side effects, they are not primarily known for causing B-cell depletion or an increased risk of PML like rituximab.
*Topoisomerase II inhibitor*
- **Topoisomerase II inhibitors** (e.g., etoposide, doxorubicin) are chemotherapy agents that induce DNA damage.
- Their primary toxicities include myelosuppression, cardiotoxicity (for anthracyclines), and secondary malignancies, not opportunistic viral infections like PML.
*Free radical formation*
- **Free radical formation** is a mechanism of action for certain chemotherapeutic agents like **bleomycin** or **anthracyclines**, which cause DNA damage.
- While these drugs have significant side effects, they are not typically linked to the selective immunosuppression that leads to PML in the context of CLL treatment.
Question 53: A 24-year-old man presents with difficulty breathing and blurred vision in the left eye. No significant past medical history or current medications. He has had more than 6 sexual partners (both men and women) and did not use any form of protection during sexual intercourse. No significant family history. Upon physical examination, the patient has crackles in all lobes bilaterally. Ophthalmologic exam reveals a single white lesion in the left eye with an irregular, feathery border, as well as evidence of retinal edema and necrosis. A rapid HIV test is positive. What is the mechanism of action of the drug that can be given to treat the ocular symptoms in this patient?
A. Inhibits A-site tRNA binding during translation
B. Guanosine analog that preferably inhibits viral DNA polymerase (Correct Answer)
C. Blocks CCR5 receptor preventing viral entry
D. A neuraminidase inhibitor preventing release of viral progeny
E. Prevents viral uncoating
Explanation: **Guanosine analog that preferably inhibits viral DNA polymerase**
* The clinical presentation (difficulty breathing, bilateral crackles, blurred vision, retinal lesion, and positive HIV test in a young, promiscuous male) is highly suggestive of **Cytomegalovirus (CMV) retinitis**, a common opportunistic infection in advanced HIV.
* The primary treatment for CMV retinitis is **ganciclovir**, which acts as a guanosine analog and selectively inhibits viral DNA polymerase, preventing CMV replication.
* *Inhibits A-site tRNA binding during translation*
* This mechanism of action describes the antibiotic **tetracycline**, which targets bacterial ribosomes.
* It is not relevant for the treatment of a viral infection like CMV.
* *Blocks CCR5 receptor preventing viral entry*
* This mechanism describes **maraviroc**, an antiretroviral drug used to treat HIV by preventing the virus from entering CD4+ cells.
* While the patient is HIV positive, this mechanism does not directly address the *ocular symptoms* caused by CMV.
* *A neuraminidase inhibitor preventing release of viral progeny*
* This mechanism describes drugs like **oseltamivir** and **zanamivir**, which are used to treat influenza by inhibiting the release of new viral particles.
* It is not indicated for the treatment of CMV infection.
* *Prevents viral uncoating*
* This mechanism is characteristic of **amantadine** and **rimantadine**, which are used to treat influenza A by interfering with the uncoating process of the virus.
* This mechanism does not apply to CMV treatment.
Question 54: A public health researcher is invited to participate in a government meeting on immunization policies. Other participants in the meeting include physicians, pediatricians, representatives of vaccine manufacturers, persons from the health ministry, etc. For a specific viral disease, there are 2 vaccines - one is a live attenuated vaccine (LAV) and the other is a subunit vaccine. Manufacturers of both the vaccines promote their own vaccines in the meeting. Non-medical people in the meeting ask the public health researcher to compare the 2 types of vaccines objectively. The public health researcher clearly explains the pros and cons of the 2 types of vaccines. Which of the following statements is most likely to have been made by the public health researcher in his presentation?
A. LAV produces poorer immunological memory than a subunit vaccine as the later contains only specific immunogenic antigens
B. LAV cannot cause symptomatic infection in an immunocompetent person and, therefore, is as safe as a subunit vaccine
C. LAV is equally safe as a subunit vaccine for administration to a pregnant woman
D. LAV has less potential for immunization errors as compared to a subunit vaccine
E. LAV requires stricter requirements for cold chain maintenance as compared to a subunit vaccine (Correct Answer)
Explanation: ***LAV requires stricter requirements for cold chain maintenance as compared to a subunit vaccine***
- Live attenuated vaccines (LAVs) contain live, albeit weakened, viruses that can "die" if not stored properly, making them exceptionally **sensitive to temperature fluctuations** and requiring a stringent **cold chain** for stability.
- Subunit vaccines, consisting of isolated viral components, are generally more **thermally stable** and have less demanding storage requirements, simplifying logistics.
*LAV produces poorer immunological memory than a subunit vaccine as the later contains only specific immunogenic antigens*
- This statement is incorrect as LAVs typically induce a **robust and long-lasting immune response** resembling natural infection, including strong cellular and humoral immunity and excellent immunological memory.
- Subunit vaccines often require **multiple doses and adjuvants** to achieve a comparable, though sometimes less comprehensive, immune memory.
*LAV cannot cause symptomatic infection in a immunocompetent person and, therefore, is as safe as a subunit vaccine*
- This statement is false because while rare, LAVs can cause **mild, self-limiting infections** in immunocompetent individuals and can lead to more serious, even **symptomatic, disease in immunocompromised** individuals due to residual virulence.
- Subunit vaccines, containing only specific antigens, **cannot replicate** and thus pose no risk of causing infection, making them generally safer for vulnerable populations.
*LAV is equally safe as a subunit vaccine for administration to a pregnant woman*
- This statement is incorrect; LAVs are generally **contraindicated in pregnant women** due to the theoretical, albeit minimal, risk of **fetal infection** from the replicating attenuated virus.
- Subunit vaccines are generally considered **safe for use during pregnancy** as they contain no live virus and cannot cause infection in the mother or fetus.
*LAV has a less potential for immunization errors as compared to a subunit vaccine*
- This statement is incorrect. Both vaccine types can be subject to immunization errors, but LAVs can have unique errors such as **improper reconstitution** or administration to contraindicated individuals, leading to potential adverse events.
- Subunit vaccines, while also susceptible to administration errors, generally have a **lower risk of severe outcomes** from such errors due to their non-replicating nature.
Question 55: A 39-year-old man comes to the physician because of a 4-month history of fatigue. During this period, he has also had a 7.7-kg (17-lb) weight loss, despite having a normal appetite. He is sexually active with 3 female partners and uses condoms inconsistently. An HIV screening test and confirmatory test are both positive. CD4+ T-lymphocyte count is 570/mm3 (N ≥ 500) and the viral load is 104 copies/mL. Treatment with lamivudine, zidovudine, and indinavir is begun. The patient is most likely to experience which of the following adverse effects?
A. Pancreatitis
B. Urolithiasis (Correct Answer)
C. Stevens-Johnson syndrome
D. Hepatotoxicity
E. Hyperpigmentation of palms and soles
Explanation: ***Urolithiasis***
- **Indinavir**, a **protease inhibitor**, is known to cause **crystalluria** and **nephrolithiasis** (kidney stones) in a significant number of patients due to its poor solubility in urine.
- Patients on indinavir therapy are often advised to drink plenty of fluids to prevent stone formation.
*Pancreatitis*
- While some antiretroviral drugs, particularly **didanosine** (a nucleoside reverse transcriptase inhibitor), can cause pancreatitis, it is not a primary adverse effect of the specific combination given (lamivudine, zidovudine, indinavir).
- Lamivudine and zidovudine generally have a lower risk of pancreatitis compared to didanosine.
*Stevens-Johnson syndrome*
- This severe cutaneous reaction is more commonly associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) like **nevirapine** or certain sulfonamides, but not typically with indinavir or the NRTIs lamivudine and zidovudine.
- It involves widespread blistering and shedding of the skin and mucous membranes.
*Hepatotoxicity*
- Hepatotoxicity can occur with many antiretroviral drugs, especially NNRTIs (e.g., nevirapine) and some protease inhibitors, but it's not the *most likely* adverse effect for *indinavir* specifically.
- The combination used does not have hepatotoxicity as its most prominent or common severe side effect.
*Hyperpigmentation of palms and soles*
- This side effect, often referred to as **zebrafish skin**, is primarily associated with **zidovudine** (an NRTI), but typically involves the nails and mucous membranes more prominently than palms and soles.
- While possible, indinavir's unique adverse effect of urolithiasis is more distinct and directly related to the drug's properties.
Question 56: A 17-year-old girl presents to the emergency department with a severe headache. The patient has had headaches in the past, but she describes this as the worst headache of her life. Her symptoms started yesterday and have been getting progressively worse. The patient states that the pain is mostly on one side of her head. There has been a recent outbreak of measles at the patient’s school, and the patient’s mother has been trying to give her daughter medicine to prevent her from getting sick, but the mother fears that her daughter may have caught the measles. On physical exam, you note an obese young girl who is clutching her head with the light in the room turned off. Her neurological exam is within normal limits. Fundoscopic exam reveals mild bilateral papilledema. A MRI of the head is obtained and reveals cerebral edema. A lumbar puncture reveals an increased opening pressure with a normal glucose level. Which of the following is the most likely diagnosis?
A. Bacterial meningitis
B. Fat-soluble vitamin overuse (Correct Answer)
C. Viral meningitis
D. Subarachnoid hemorrhage
E. Migraine headache
Explanation: ***Fat-soluble vitamin overuse***
- The patient's history of her mother giving her daughter medicine to prevent her from getting sick, combined with symptoms like **papilledema** and elevated **intracranial pressure (ICP)**, strongly suggests **vitamin A toxicity**.
- **Pseudotumor cerebri (idiopathic intracranial hypertension)**, often induced by vitamin A overuse, manifests with severe headaches, papilledema, and normal CSF glucose.
*Bacterial meningitis*
- Would typically present with **fever**, **nuchal rigidity**, and altered mental status, which are not described.
- Lumbar puncture would show **decreased glucose** and **elevated protein** in the cerebrospinal fluid.
*Viral meningitis*
- While it can cause headaches and photophobia, **papilledema** and chronic worsening symptoms are less typical.
- Cerebrospinal fluid analysis would show **normal glucose** but usually **elevated lymphocytes**, which isn't explicitly mentioned here.
*Subarachnoid hemorrhage*
- Characteristically causes a sudden onset "thunderclap" headache, often with **meningeal irritation** and neurological deficits.
- Cerebrospinal fluid would typically contain **xanthochromia** (yellow discoloration due to bilirubin), which is not present.
*Migraine headache*
- Although it fits the description of a severe, unilateral headache with **photophobia**, it does not explain the **papilledema** or elevated intracranial pressure.
- Migraines are not typically associated with cerebral edema on MRI.
Question 57: A 61-year-old woman presents to her primary care physician complaining of left-sided facial pain that started yesterday. She describes the pain as stinging, burning, and constant. It does not worsen with jaw movement or chewing. Her past medical history includes hyperlipidemia and multiple sclerosis (MS), and she had chickenpox as a child but received a shingles vaccination last year. Medications include simvastatin and glatiramer acetate. The patient’s last MS flare was 5 weeks ago, at which time she received a prednisone burst with taper. At this visit, her temperature is 99.9 °F (37.7°C), blood pressure is 139/87 mmHg, pulse is 82/min, and respirations are 14/min. On exam, there is no rash or skin change on either side of the patient’s face. Gentle palpation of the left cheek and mandible produce significant pain, but there is full range of motion in the jaw. Which of the following medications is the most likely to prevent long-term persistence of this patient’s pain?
A. Carbamazepine
B. Topical corticosteroids
C. Oral acyclovir (Correct Answer)
D. Amitriptyline
E. Gabapentin
Explanation: ***Oral acyclovir***
- The patient's symptoms (stinging, burning, constant facial pain, history of chickenpox, recent MS flare, and prednisone use) are highly suggestive of a **herpes zoster (shingles) reactivation**, despite prior vaccination. Early antiviral therapy, such as oral acyclovir, is crucial to reduce the duration and severity of the acute pain and, more importantly, to prevent **postherpetic neuralgia (PHN)**.
- Starting acyclovir within 72 hours of symptom onset significantly decreases the risk of developing long-term pain complications like PHN by inhibiting viral replication and reducing nerve damage.
*Carbamazepine*
- This medication is a first-line treatment for **trigeminal neuralgia**, characterized by brief, excruciating, shock-like pain triggered by specific stimuli, which differs from the patient's constant burning pain.
- While it can manage neuropathic pain, it does not address the underlying viral cause of herpes zoster and will not prevent PHN.
*Topical corticosteroids*
- Topical corticosteroids are primarily used to reduce **inflammation and itching** associated with skin rashes, such as those that may occur with herpes zoster.
- They do not possess antiviral properties and therefore will not *prevent* the long-term neurological complication of PHN.
*Amitriptyline*
- Amitriptyline, a tricyclic antidepressant, is a common treatment for **postherpetic neuralgia** once it has already developed, as well as other neuropathic pain conditions.
- However, it is not used to prevent the development of PHN in the acute phase of a herpes zoster infection; early antiviral treatment is the preventative strategy.
*Gabapentin*
- Gabapentin is an effective medication for established **neuropathic pain**, including postherpetic neuralgia.
- Similar to amitriptyline, gabapentin treats the *symptoms* of PHN once it is present but does not prevent its occurrence when used during the acute viral stage.
Question 58: A 67-year-old man presents to the emergency department with confusion. The patient is generally healthy, but his wife noticed him becoming progressively more confused as the day went on. The patient is not currently taking any medications and has no recent falls or trauma. His temperature is 102°F (38.9°C), blood pressure is 126/64 mmHg, pulse is 120/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam is notable for a confused man who cannot participate in a neurological exam secondary to his confusion. No symptoms are elicited with flexion of the neck and jolt accentuation of headache is negative. Initial laboratory values are unremarkable and the patient's chest radiograph and urinalysis are within normal limits. An initial CT scan of the head is unremarkable. Which of the following is the best next step in management?
A. CT angiogram of the head and neck
B. Vancomycin, ceftriaxone, ampicillin, and dexamethasone
C. Acyclovir (Correct Answer)
D. PCR of the cerebrospinal fluid
E. MRI of the head
Explanation: ***Acyclovir***
- This patient presents with **acute confusion and fever** without an obvious infectious source, negative meningeal signs, and normal initial imaging, highly suggestive of **herpes simplex encephalitis (HSE)**.
- HSE is a **medical emergency** with high mortality (70-80%) if untreated, but mortality drops to 20-30% with early acyclovir therapy.
- **Empiric acyclovir must be started immediately** upon clinical suspicion of HSE, **without waiting for diagnostic confirmation**.
- Standard management includes obtaining CSF for PCR **concurrently** with starting acyclovir, but treatment should never be delayed for diagnostic testing.
- The best next step in **management** is initiating acyclovir; CSF PCR is obtained for confirmation but does not delay treatment.
*PCR of the cerebrospinal fluid*
- **CSF PCR for HSV** is the gold standard **diagnostic test** for HSE with high sensitivity (96%) and specificity (99%).
- While lumbar puncture should be performed to obtain CSF for PCR, this is a **diagnostic step** that should be done **concurrently** with starting acyclovir, not instead of it.
- The question asks for best next step in **management**, not diagnosis—acyclovir therapy takes precedence.
- Delaying acyclovir while awaiting diagnostic confirmation significantly increases morbidity and mortality.
*Vancomycin, ceftriaxone, ampicillin, and dexamethasone*
- This broad-spectrum antibiotic regimen is empiric therapy for **bacterial meningitis** and should be considered in patients with fever and altered mental status.
- However, the **absence of meningeal signs** (negative nuchal rigidity, negative jolt accentuation) makes bacterial meningitis less likely.
- In practice, when HSE is suspected but bacterial meningitis cannot be excluded, both antimicrobial regimens may be initiated empirically, but the primary concern here is HSE given the clinical presentation.
*MRI of the head*
- **MRI with FLAIR sequences** is highly sensitive for HSE and typically shows **temporal lobe involvement** (especially medial temporal lobes).
- However, MRI findings may be **normal early in the disease course** (first 48-72 hours).
- MRI is useful for supporting the diagnosis but should **not delay empiric acyclovir therapy**.
- Obtaining MRI before treatment would be inappropriate given the time-sensitive nature of HSE.
*CT angiogram of the head and neck*
- CT angiography evaluates vascular structures and is indicated for suspected **stroke, aneurysm, or vascular dissection**.
- This patient lacks focal neurological deficits, signs of acute stroke, or vascular risk factors that would prioritize vascular imaging.
- The presentation with fever and diffuse encephalopathy points toward an infectious/inflammatory process rather than a vascular etiology.
Question 59: A 22-year-old man comes to the physician for a follow-up evaluation for chronic lower back pain. He has back stiffness that lasts all morning and slowly improves throughout the day. He has tried multiple over-the-counter medications, including ibuprofen, without any improvement in his symptoms. Physical examination shows tenderness over the iliac crest bilaterally and limited range of motion of the lumbar spine with forward flexion. The results of HLA-B27 testing are positive. An x-ray of the lumbar spine shows fusion of the lumbar vertebrae and sacroiliac joints. The physician plans to prescribe a new medication but first orders a tuberculin skin test to assess for the risk of latent tuberculosis reactivation. Inhibition of which of the following is the most likely primary mechanism of action of this drug?
A. mTOR kinase
B. Calcineurin
C. NF-κB
D. Inosine monophosphate dehydrogenase
E. TNF-α (Correct Answer)
Explanation: **TNF-α**
- The clinical presentation with **chronic lower back pain**, morning stiffness, **limited lumbar spine range of motion**, positive **HLA-B27**, and **fusion of lumbar vertebrae and sacroiliac joints** is highly suggestive of **ankylosing spondylitis**.
- Biologic medications, specifically **TNF-α inhibitors**, are a cornerstone of treatment for ankylosing spondylitis, especially when conventional therapies like NSAIDs fail. The mention of screening for latent tuberculosis reactivation strongly points to the use of a TNF-α inhibitor, as these drugs increase the risk of TB reactivation.
*mTOR kinase*
- **mTOR inhibitors** (e.g., sirolimus, everolimus) are primarily used as **immunosuppressants** in organ transplantation and in some cancers.
- They are not a first-line or common treatment for ankylosing spondylitis or other spondyloarthropathies.
*Calcineurin*
- **Calcineurin inhibitors** (e.g., cyclosporine, tacrolimus) are potent **immunosuppressants** used in transplant rejection prevention and some autoimmune diseases.
- While they can have immunosuppressive effects, they are not the primary target for the treatment of ankylosing spondylitis.
*NF-κB*
- **NF-κB** is a crucial transcription factor involved in inflammation and immune responses. While relevant to inflammatory conditions, directly targeting NF-κB is not the primary mechanism of action for the most effective biologic therapies used in ankylosing spondylitis.
- **Glucocorticoids** can inhibit NF-κB, but they are not the main long-term treatment for ankylosing spondylitis, and the context points to a biologic.
*Inosine monophosphate dehydrogenase*
- **Inosine monophosphate dehydrogenase (IMPDH) inhibitors** (e.g., mycophenolate mofetil) block purine synthesis, thus inhibiting lymphocyte proliferation.
- These drugs are used in **transplantation** and some **autoimmune diseases** (e.g., lupus, vasculitis) but are not typically used for ankylosing spondylitis.
Question 60: A 26-year-old man comes to the physician for a follow-up examination. He was diagnosed with HIV infection 2 weeks ago. His CD4+ T-lymphocyte count is 162/mm3 (N ≥ 500). An interferon-gamma release assay is negative. Prophylactic treatment against which of the following pathogens is most appropriate at this time?
A. Cytomegalovirus
B. Toxoplasma gondii
C. Mycobacterium tuberculosis
D. Aspergillus fumigatus
E. Pneumocystis jirovecii (Correct Answer)
Explanation: ***Pneumocystis jirovecii***
- This patient's **CD4+ T-lymphocyte count of 162/mm3** is below the threshold of 200/mm3, indicating a significant risk for **Pneumocystis pneumonia (PCP)**, an opportunistic infection in HIV.
- Prophylaxis with **trimethoprim-sulfamethoxazole (TMP-SMX)** is highly effective and recommended for HIV patients with CD4 counts less than 200/mm3.
*Cytomegalovirus*
- **CMV prophylaxis** is generally not recommended for all HIV patients, even with low CD4 counts, unless there is evidence of active disease or extremely low CD4 counts (e.g., <50/mm3) with high viral loads.
- While CMV can cause end-organ disease in advanced HIV, routine primary prophylaxis is not standard for this CD4 level.
*Toxoplasma gondii*
- **Toxoplasma prophylaxis** is indicated for HIV patients with **CD4 counts less than 100/mm3** who are also seropositive for *Toxoplasma gondii*.
- The patient's CD4 count is 162/mm3, and there's no mention of *Toxoplasma* serostatus, making it less appropriate than PCP prophylaxis.
*Mycobacterium tuberculosis*
- The patient's **interferon-gamma release assay (IGRA) is negative**, which suggests no **latent tuberculosis infection (LTBI)**, thus making primary prophylaxis unnecessary at this time.
- While HIV patients are at high risk for TB, prophylaxis is typically given for LTBI or as secondary prophylaxis for those who have completed treatment for active TB.
*Aspergillus fumigatus*
- **Aspergillus infections** are typically seen in patients with severe **neutropenia** or those receiving high-dose corticosteroids, not primarily in HIV patients based solely on CD4 count.
- Routine prophylaxis for Aspergillus is not recommended for HIV patients, even with low CD4 counts, unless there is a specific risk factor.
