WBR0235

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Microbiology, MainCategory::Pharmacology
Sub Category	SubCategory::Neurology, SubCategory::General Principles
Prompt	[[Prompt::A 16-year-old boy is brought to his physician's clinic by his father. Over the past several days, the patient has been increasingly fatigued and has noticed that the left side of his face has become paralyzed and less expressive. He denies any sick contacts or recent changes in mood, appetite, or weight. The patient states that he recently returned from a trip with the local boy scouts approximately 1 months ago. The patient explains that at first he saw a red lesion with a central clearing in his left lower extremity, but the lesion self-resolved without any intervention. In the clinic, neurological exam is significant only for unilateral weakness of the facial muscles on the left side. Further work-up, including CSF analysis, yields normal results. The physician then prescribes a pharmacologic agent to treat the patient's condition. What is the mechanism of action of the prescribed pharmacologic agent?]]
Answer A	AnswerA::Tissue plasminogen activator
Answer A Explanation	[[AnswerAExp::TpA may be indicated for specific cases of ischemic stroke or myocardial infarction (MI). While a stroke may produce unilateral neurologic symptoms, stroke is far less likely than Lyme disease in a young patient who has recently returned from a camping trip.]]
Answer B	AnswerB::Nucleotide analogue
Answer B Explanation	AnswerBExp::Acyclovir is a nucleotide analogue that inhibits HSV replication. HSV can cause facial palsy, but it is a less common cause of facial palsy than Lyme disease, especially in a patient who has recently returned from a camping trip.
Answer C	AnswerC::Antithrombin III activator
Answer C Explanation	AnswerCExp::Heparin activates antithrombin III. Heparin is indicated for thromboembolic diseases, which are less likely than Lyme disease in a young patient who has recently returned from a camping trip.
Answer D	AnswerD::Topoisomerase inhibitor
Answer D Explanation	AnswerDExp::Fluoroquinolones are antibiotics that act by inhibiting topoisomerase activity. However, fluoroquinolones are not the optimal pharmacologic therapy to treat Lyme disease.
Answer E	AnswerE::Inhibitor of aminoacyl tRNA entry into ribosome
Answer E Explanation	AnswerEExp::Tetracyclines are antibiotics that act by inhibiting aminoacyl tRNA entry into ribosome. Tetracyclines are the optimal pharmacologic therapy to treat Lyme disease in adult patients.
Right Answer	RightAnswer::E
Explanation	[[Explanation::Lyme disease is a multi-organ disease that involves the skin, nervous system, the heart, and the musculoskeletal system. It is an infectious disease caused by the spirochete Borrelia burgdorferi, whose natural reservoir is mainly mice. B. burgdorferi is transmitted to humans by Ixodes tick bite. Characteristically, tick bites are non-painful, and ticks may persist on human skin for several days. For transmission of the infection to occur, the tick needs to bite the skin for at least one day. Lyme disease is a common infection in Europe and Northeast USA during the summer and spring. Lyme disease may be classified clinically into 3 stages based on chronological progression: Early Lyme disease: Characterized by erythema migrans (bull's eye lesion), which is the pathognomonic skin lesion of early Lyme disease. Onset is usually between 3 and 30 days following tick bite. The most common location of erythema migrans is the lower extremities and the trunk. Patients with typical erythema migrans are generally administered empirical doxycycline with no need for further diagnostic work-up. Secondary (disseminated) Lyme disease: Characterized by the presence of neurological, cardiac, and rheumatic manifestations that may present anytime within weeks to several months (typically up to 6 months). Neurological manifestations include meningitis, encephalitis, radicular pains, flaccid palsy, and sensory abnormalities. Cardiac manifestations usually appear earlier than neurological manifestations and include atrioventricular blocks, pericarditis, and rarely, pancarditis. Finally, rheumatic manifestations include bone and joint pain with possible edema and effusions of the large joints. Tertiary (chronic) Lyme disease: Characterized by chronic symptoms that are usually present several after following an infection that was not adequately treated. Manifestations may include persistent join pain and edema, chronic progressive encephalomyelitis, memory impairment, and chronic peripheral neuropathy. Chronic Lyme disease may be present even when the organism that caused the initial infection has been cleared. The diagnosis of Lyme disease is made clinically when patients report exposure to ticks and present with typical erythema migrans on physical examination. In contrast, disseminated disease is more difficult to diagnose, and serological testing is necessary with a two-step approach: First, a high-sensitivity ELISA (sensitive) followed by Western blot assay (specific) if ELISA yields positive results. IgM levels typically start to appear 2-4 weeks after infection. Early Lyme disease, early disseminated disease, and Lyme disease with cranial nerve palsy but normal CSF work-up are optimally treated with tetracycline antibiotics (eg doxycyline). Tetracyclines act by blocking entry of aminoacyl tRNAs into the bacterial ribosome, thereby inhibiting protein synthesis. Tetracyclines are contraindicated in children < 8 years of age, pregnant, and lactating women due to its association with teeth discoloration. Instead, these patients should be prescribed amoxicillin, which is the second-line agent for treatment of Lyme disease. Educational Objective: Tetracyclines are antibiotics that act by inhibiting aminoacyl tRNA entry into ribosome. Tetracyclines are the optimal pharmacologic therapy to treat Lyme disease in adult patients. References: Biesiada G, Czepiel J, Lesniak MR, et al. Lyme disease: a review. Arch Med Sci. 2012;8(6):978-82. First Aid 2014 page 141]]
Approved	Approved::Yes
Keyword	WBRKeyword::Lyme disease, WBRKeyword::Lyme, WBRKeyword::Borrelia burgdorferi, WBRKeyword::Bacteria, WBRKeyword::Zoonotic bacteria, WBRKeyword::Antibiotics, WBRKeyword::Tetracycline, WBRKeyword::Mechanism of action, WBRKeyword::Facial palsy, WBRKeyword::Palsy
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