A 74-year-old woman with no significant past medical history presents with 1 week of fever, unremitting headache and hip and shoulder stiffness. She denies any vision changes. Physical examination is remarkable for right scalp tenderness and range of motion is limited due to pain and stiffness. Neurological testing is normal. Laboratory studies are significant for an erythrocyte sedimentation rate (ESR) at 75 mm/h (normal range 0-22 mm/h for women). Which of the following is the most appropriate next step in management?

Obtain CT head without contrast

Perform a temporal artery biopsy

A 25-year-old man of Mediterranean descent makes an appointment with his physician because his skin and sclera have become yellow. He complains of fatigue and fever that started at the same time icterus appeared. On examination, he is tachycardic and tachypneic. The oxygen (O2) saturation is < 90%. He has increased unconjugated bilirubin, hemoglobinemia, and an increased number of reticulocytes in the peripheral blood. What is the most likely diagnosis?

Hemolytic anemia caused by glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency)

Microcytic anemia caused by iron deficiency

Autoimmune hemolytic anemia (AIHA)

A 5-year-old boy is brought to see his pediatrician because of painless swelling in both legs and around his eyes. His mother reports that it is worse in the morning and these symptoms have started 4 days ago. The child has just recovered from a severe upper respiratory tract infection 8 days ago. The boy was born at 39 weeks gestation via spontaneous vaginal delivery. He is up to date on all vaccines and is meeting all developmental milestones. Today, his blood pressure is 110/65 mm Hg, the heart rate is 90/min, the respiratory rate is 22/min, and the temperature is 36.8°C (98.2°F). On physical examination, his face is edematous and there is a 2+ pitting edema over both legs up to his hips. Laboratory results are shown. Serum albumin 2.4 g/dL Serum triglycerides 250 mg/dL Serum cholesterol 300 mg/dL Urine dipstick 4+ protein Which of the following is the best initial therapy for this patient’s condition?

Prednisolone and cyclophosphamide

A 1-month-old boy is brought in by his mother for episodes of “not breathing.” She reports noticing that the patient will occasionally stop breathing while he’s sleeping, and that these episodes have been occurring more frequently. The patient was born at 32 weeks due to placental insufficiency. He was in the neonatal intensive care unit for 1 day to be placed on a respirator. During prenatal testing, it was revealed that the mother was not immune to rubella, but she otherwise had an uncomplicated pregnancy. She has no medical conditions and took only prenatal vitamins. The patient has a 3-year-old sister who is healthy. His father has a “heart condition.” The patient’s temperature is 98°F (36.7°C), blood pressure is 91/55 mmHg, pulse is 207/min, and respirations are 50/min with an oxygen saturation of 97% on room air. Physical examination is notable for pale conjunctiva. Labs are obtained, as shown below: Leukocyte count: 10,000/mm^3 with normal differential Hemoglobin: 8.2 g/dL Hematocrit: 28% Mean corpuscular volume (MCV): 100 um^3 Platelet count: 300,000/mm^3 Reticulocyte count: 0.8% (normal range: 2-6%) Lactate dehydrogenase: 120 U/L (normal range: 100-250 U/L) A peripheral smear reveals normocytic and normochromic red blood cells. Which of the following is a mechanism for the patient’s most likely diagnosis?

Impaired erythropoietin production

Minor blood group incompatibility

A 4-year-old boy is brought to a pediatrician by his parents with a history of fever for the last 5 days and irritability, decreased appetite, vomiting, and swelling of the hands and feet for the last 3 days. The patient’s mother mentions that he has been taking antibiotics and antipyretics prescribed by another physician for the last 3 days, but there has been no improvement His temperature is 39.4°C (103.0°F), pulse is 128/min, respiratory rate is 24/min, and blood pressure is 96/64 mm Hg. On physical examination, there is significant edema of the hands and feet bilaterally. There is a 2.5 cm diameter freely moveable, nontender cervical lymph node is palpable on the right side. A strawberry tongue and perianal erythema are noted. Conjunctival injection is present bilaterally. Laboratory findings reveal mild anemia and a leukocytosis with a left-shift. Erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) are increased. If not treated appropriately, this patient is at increased risk of developing which of the following complications?

Lower gastrointestinal hemorrhage

Acute disseminated encephalomyelitis (ADEM)

A 5-year-old girl presents with a rash and a persistent fever of 41.0°C (105.8°F), not relieved by Tylenol. The patient's mother says that her symptoms started 5 days ago and have not improved. The rash started on her trunk and now is present everywhere including the palms and soles. Her birth history is normal. Her pulse is 120/min and respiratory rate is 22/min. On physical examination, the patient is agitated and ill-appearing. There is significant swelling of the distal upper and lower extremities bilaterally. The pharynx is hyperemic (see image). Generalized edema with palpable cervical lymphadenopathy is noted. Muscle tone is normal. Remainder of exam is unremarkable. Laboratory findings are significant for the following: Laboratory test Hb 9 g/dL RBC 3.3/mm3 Neutrophilic leukocytosis 28,000/mm3 Normal platelet count 200,000/mm3 Serum ɣ-GT increased Hyperbilirubinemia 2.98 mg/dL AST and ALT are normal, but there is markedly increased serum CRP. Which of the following is the most likely diagnosis in this patient?

Staphylococcal scalded skin syndrome

A previously healthy 4-year-old boy is brought to the physician by his parents because he has had a fever, diffuse joint pain, and a rash on his abdomen for the past week. Acetaminophen did not improve his symptoms. He emigrated from China with his family 2 years ago. He attends daycare. His immunization records are not available. His temperature is 38.5°C (101.3°F), pulse is 125/min, and blood pressure is 100/60 mm Hg. Examination shows polymorphous truncal rash. The eyes are pink with no exudate. The tongue is shiny and red, and the lips are cracked. The hands and feet are red and swollen. There is right-sided anterior cervical lymphadenopathy. Which of the following is the most appropriate next step in management?

HHV-6 immunoglobulin M (IgM) detection

Antistreptolysin O titer measurement

Acute phase management — USMLE Lesson

Diagnosis - Spotting the Fire

Based on clinical criteria; lab tests are supportive, not diagnostic.

📌 Mnemonic: CRASH & Burn

Fever > 5 days ("Burn") PLUS ≥ 4 of the following:
- Conjunctivitis: Bilateral, non-purulent.
- Rash: Polymorphous, generalized.
- Adenopathy: Cervical, unilateral, >1.5 cm.
- Strawberry tongue & lip changes (redness, fissures).
- Hand & foot changes: Erythema, edema (acute); periungual desquamation (subacute).

Kawasaki Disease: Clinical Signs Collage

⭐ Atypical/Incomplete KD: Suspect in infants with prolonged unexplained fever, even with <4 criteria. Echocardiography is crucial for diagnosis and assessing coronary artery involvement.

Initial Workup - The Lab Clues

Acute Phase Reactants:
- ↑ ESR (often >100 mm/hr)
- ↑ CRP (>3 mg/dL)
Complete Blood Count (CBC):
- Leukocytosis (>15,000/μL) with neutrophilia.
- Normocytic, normochromic anemia.
- Platelets: Normal or ↓ initially, then marked thrombocytosis from week 2.
Other Key Labs:
- ↑ Transaminases (ALT)
- ↓ Albumin (<3 g/dL)
- Sterile pyuria
- CSF: Aseptic meningitis (pleocytosis)

⭐ Thrombocytosis is the most striking feature, typically appearing in the 2nd week. Platelet counts can rise to > 10 lakh/mm³.

First-Line Tx - Dousing the Flames

Goal: Rapidly control inflammation to prevent coronary artery aneurysms (CAA).
Administer within 10 days of fever onset for maximal efficacy.
Dual Therapy:
- Intravenous Immunoglobulin (IVIG):
  - The cornerstone of treatment.
  - Single large dose of 2 g/kg infused over 10-12 hours.
- Aspirin (ASA):
  - Initially high-dose for anti-inflammatory effect: 80-100 mg/kg/day.
  - After patient is afebrile for 48-72 hours, reduce to a low anti-platelet dose: 3-5 mg/kg/day.

⭐ Treatment with IVIG within the first 10 days of illness reduces the incidence of coronary artery aneurysms from 25% to less than 5%.

Management of Persistent Fever:

Refractory KD - Stubborn Embers

Defined as persistent or recrudescent fever ≥ 36-48h after completing initial IVIG infusion. Occurs in 10-20% of patients, carrying a higher risk of coronary artery aneurysms (CAA).

Coronary artery aneurysm in Kawasaki Disease

Management Algorithm:

⭐ Infliximab is often preferred in patients with high-risk lab markers (e.g., ↑CRP, ↑Ferritin) or early signs of CAA, as it may reduce coronary artery inflammation more rapidly than corticosteroids.

High‑Yield Points - ⚡ Biggest Takeaways

IVIg (2 g/kg single dose) is the cornerstone of acute management, best given within 10 days of fever onset.

Initial treatment includes high-dose aspirin (80-100 mg/kg/day) to rapidly control systemic inflammation.

Aspirin is switched to a low, antiplatelet dose (3-5 mg/kg/day) once afebrile for 48-72 hours.

The primary goal is preventing coronary artery aneurysms, the most feared complication.

Baseline echocardiography is mandatory to assess for early cardiac changes.

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