A 23-year-old woman presents with progressively worsening headache, photophobia, and intermittent fever that have lasted for 6 days. She says her headache is mostly frontal and radiates down her neck. She denies any recent history of blood transfusions, recent travel, or contact with animals. Her past medical history is unremarkable. She is sexually active with a single partner for the past 3 years. Her temperature is 38.5°C (101.3°F). On physical examination, she appears pale and diaphoretic. A fine erythematous rash is noted on the neck and forearms. A lumbar puncture is performed and CSF analysis reveals: Opening pressure: 300 mm H2O Erythrocytes: None Leukocytes: 72/mm3 Neutrophils: 10% Lymphocytes: 75% Mononuclear: 15% Protein: 100 mg/dL Glucose: 70 mg/dL Which of the following is the most likely diagnosis in this patient?

Lymphocytic choriomeningitis virus

A 25-year-old man presents to the emergency department after a motor vehicle accident. He was the unrestrained front seat driver in a head on collision. The patient is unresponsive and his medical history is unknown. His temperature is 99.5°F (37.5°C), blood pressure is 67/38 mmHg, pulse is 190/min, respirations are 33/min, and oxygen saturation is 98% on room air. The patient is started on IV fluids, blood products, and norepinephrine. A FAST exam is performed and a pelvic binder is placed. One hour later, his temperature is 98.3°F (36.8°C), blood pressure is 119/66 mmHg, pulse is 110/min, respirations are 15/min, and oxygen saturation is 97% on room air. The patient is currently responsive. Management of the patient's pelvic fracture is scheduled by the orthopedic service. While the patient is waiting in the emergency department he suddenly complains of feeling hot, aches, and a headache. The patient's temperature is currently 101°F (38.3°C). He has not been given any pain medications and his past medical history is still unknown. Which of the following is the most likely diagnosis?

Febrile non-hemolytic transfusion reaction

Acute hemolytic transfusion reaction

Minor blood group incompatibility

A 61-year-old woman comes to the physician because of a 6-month history of left knee pain and stiffness. Examination of the left knee shows tenderness to palpation along the joint line; there is crepitus with full flexion and extension. An x-ray of the knee shows osteophytes with joint-space narrowing. Arthrocentesis of the knee joint yields clear fluid with a leukocyte count of 120/mm3. Treatment with ibuprofen during the next week significantly improves her condition. The beneficial effect of this drug is most likely due to inhibition of which of the following?

Conversion of arachidonic acid to prostaglandin G2

Conversion of hypoxanthine to urate

Conversion of phospholipids to arachidonic acid

Conversion of prostaglandin H2 to thromboxane A2

Conversion of dihydroorotate to orotate

A 42-year-old man undergoes therapeutic hypothermia (target temperature 33°C/91.4°F) following cardiac arrest with return of spontaneous circulation. During the cooling phase, he develops shivering, which increases oxygen consumption and interferes with target temperature achievement. He is already on sedation and neuromuscular blockade is being considered. Evaluate the most appropriate management strategy considering both efficacy and safety.

Increase sedation and add surface counter-warming of extremities before neuromuscular blockade

Administer meperidine alone to reduce shivering threshold

Abandon therapeutic hypothermia due to complications

Use only mechanical restraints to prevent movement

Immediate neuromuscular blockade without additional measures

A 72-year-old woman with end-stage renal disease on hemodialysis develops fever (103°F/39.4°C) with rigors during dialysis. Blood cultures from both the dialysis catheter and peripheral site grow gram-positive cocci. Despite appropriate antibiotics and catheter removal, she has persistent fevers of 101-102°F (38.3-38.9°C) for 7 days. She feels better and inflammatory markers are decreasing. Evaluate the most likely explanation for persistent fever.

Appropriate lag in temperature resolution despite adequate treatment

Undrained abscess requiring surgical intervention

Drug fever from antibiotic therapy

Inadequate dialysis causing uremic fever

Antibiotic-resistant organism requiring regimen change

A 19-year-old man at a rave party is brought to the ED with agitation, temperature of 107°F (41.7°C), severe hypertension (180/110 mm Hg), tachycardia, dilated pupils, and diaphoresis. His friends report he took 'Molly.' Despite aggressive cooling, his temperature remains dangerously elevated and he develops rhabdomyolysis. Evaluate the most appropriate additional pharmacologic intervention.

Benzodiazepines to reduce CNS and muscular hyperactivity

Bromocriptine as a dopamine agonist

Beta-blockers to control hypertension and tachycardia

Antipyretics to reduce hypothalamic set point

Dantrolene sodium to reduce muscle hypermetabolism

Fever patterns and significance for USMLE Step 1: High-Yield Physiology Lessons

Fever Pathophysiology - The Heat Is On

Pyrogens: Substances that cause fever.
- Exogenous: Bacterial toxins (e.g., LPS).
- Endogenous: Cytokines (IL-1, IL-6, TNF-α) released by immune cells.
Mechanism: Endogenous pyrogens act on the organum vasculosum of the lamina terminalis (OVLT) of the hypothalamus.
- This induces cyclooxygenase-2 (COX-2) to produce Prostaglandin E₂ ($PGE_2$).
- $PGE_2$ elevates the hypothalamic set-point, triggering heat production (shivering) and conservation (vasoconstriction).

⭐ NSAIDs (e.g., aspirin, ibuprofen) are antipyretic because they inhibit COX enzymes, thus blocking $PGE_2$ synthesis and resetting the hypothalamic set-point. They do not lower normal body temperature.

Fever Pathophysiology: Pyrogens to PGE2 and Antipyretics

Classic Fever Patterns - A Hot Mess

Fever patterns offer diagnostic clues by mapping temperature changes over time. While classic patterns are less common due to early antibiotic use, they remain important for specific diagnoses.

Fever patterns: intermittent, remittent, relapsing, constant

Fever Pattern	Characteristics	Classic Associations
Sustained	Temperature remains elevated with minimal fluctuation (<1°C in 24h).	Typhoid fever, Typhus, Lobar pneumonia.
Intermittent	Elevated temperature drops to normal or subnormal daily.	Malaria (Tertian/Quartan), Pyogenic infections (abscesses), Sepsis.
Remittent	Temperature fluctuates (>1°C in 24h) but never returns to normal.	Infective endocarditis, Brucellosis, many viral infections.
Relapsing	Febrile episodes are separated by days of normal temperature.	Malaria, Borreliosis (Lyme disease, Relapsing fever).

Significance & Diagnosis - Pattern Pays Off

Fever patterns offer diagnostic clues, though exceptions are common. Focus on classic textbook associations.
Continuous/Sustained: Persistently elevated with minimal fluctuation (<1°C).
- Examples: Typhoid fever, Lobar Pneumonia, Meningitis.
Remittent: Fluctuates >1°C daily but never returns to normal.
- Example: Infective Endocarditis.
Intermittent: Returns to normal at least once per 24 hours.
- Tertian (48h cycle): Malaria (P. vivax/ovale).
- Quartan (72h cycle): Malaria (P. malariae).
Relapsing: Febrile episodes separated by days of normal temperature.
- Example: Borrelia infections (e.g., Relapsing Fever).

⭐ Pel-Ebstein Fever: A classic relapsing pattern with week-long fevers followed by afebrile weeks; highly suggestive of Hodgkin Lymphoma.

High‑Yield Points - ⚡ Biggest Takeaways

Fever is mediated by PGE₂ acting on the anterior hypothalamus, which elevates the thermoregulatory set-point.

Continuous fever remains elevated with minimal fluctuation, seen in Typhoid fever.

Intermittent fever spikes and returns to normal at least once daily, typical for malaria or sepsis.

Remittent fever fluctuates but never returns to baseline, common in infective endocarditis.

Pel-Ebstein fever, a cyclical pattern of fever for days followed by afebrile periods, is classic for Hodgkin's lymphoma.

Fever of Unknown Origin (FUO) is a fever >38.3°C for >3 weeks without an identified cause.

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