What are the differential diagnoses and recommended work‑up for a 16‑year‑old male with a two‑week history of intermittent fever, an initial four‑day episode of vomiting, chills, intermittent dry headache, cough, three‑day edema and erythema of the hands and feet, and a forearm rash, now febrile?

Kawasaki Disease is the Primary Diagnosis to Rule Out Immediately

This 16-year-old male meets clinical criteria for Kawasaki disease (KD), which requires urgent diagnosis and treatment within 10 days of fever onset to prevent coronary artery aneurysms and death. The combination of prolonged fever (2 weeks), hand and foot swelling with erythema, forearm rash, and systemic symptoms strongly suggests KD, though the age is atypical 1.

Why Kawasaki Disease Must Be Considered First

The patient presents with:

• Fever >5 days (2 weeks documented)
• Extremity changes: Hand and foot swelling with redness for 3 days (acute phase erythema and edema)
• Polymorphous rash: Forearm involvement
• Systemic symptoms: Vomiting, chills, headache, cough

KD requires fever ≥5 days plus 4 of 5 principal features, OR fever plus coronary artery involvement on echocardiography 1. This patient has at least 2 confirmed features (extremity changes, rash) with fever duration met. The diagnosis can be made even if all features aren't present simultaneously—they evolve over time.

Critical Pitfall

While KD typically affects children <5 years old, adolescents can develop it and often present atypically. Do not dismiss KD based on age alone. Delayed diagnosis beyond day 10 of fever significantly increases risk of coronary complications.

Immediate Diagnostic Work-Up (Tier 1 - Urgent)

Must Obtain Today:

• 2D echocardiography - To detect coronary artery abnormalities (diagnostic even with incomplete criteria) 1
• Complete blood count - Expect thrombocytosis (later phase), leukocytosis
• ESR and CRP - Markedly elevated in KD
• Comprehensive metabolic panel - Check liver enzymes, albumin, sodium
• Troponin - Assess myocardial involvement
• BNP/NT-proBNP - Evaluate cardiac dysfunction
• Urinalysis - Sterile pyuria common in KD

Physical Examination Focus:

• Conjunctival injection - Bilateral bulbar without exudate (spares limbus)
• Oral changes - Cracked/red lips, strawberry tongue, pharyngeal erythema
• Cervical lymphadenopathy - Usually unilateral, >1.5 cm
• Cardiac examination - Gallop rhythm, murmur suggesting mitral regurgitation
• Extremities - Document exact distribution of erythema/edema; check for periungual desquamation (appears weeks 2-3)

Secondary Differential: MIS-C

Multisystem Inflammatory Syndrome in Children (MIS-C) must be excluded given overlapping features with KD 2. The presentation includes:

• Prolonged fever
• Gastrointestinal symptoms (vomiting for 4 days)
• Rash and mucocutaneous findings
• Extremity changes

Additional Testing for MIS-C:

• SARS-CoV-2 PCR and serology (IgG, IgM, IgA if available)
• Ferritin - Extreme elevation suggests MIS-C or other inflammatory conditions
• D-dimer, fibrinogen - Coagulopathy assessment
• Procalcitonin - Helps differentiate bacterial infection

MIS-C typically occurs 2-6 weeks after COVID-19 exposure and presents with more prominent GI symptoms, shock, and myocardial dysfunction than classic KD 2. The patient's 4-day vomiting episode and current systemic presentation warrant COVID testing.

Other Critical Differentials to Exclude

Infectious Causes (Rule Out First):

• Toxic shock syndrome - Check for source (wound, tampon use), hypotension, multi-organ involvement
• Scarlet fever (Group A Strep) - Rapid strep test, throat culture; sandpaper rash, strawberry tongue
• Viral exanthems - EBV, adenovirus, enterovirus serology
• Rocky Mountain spotted fever - Travel history, tick exposure; petechial rash starting at wrists/ankles
• Bacterial endocarditis - Blood cultures x3 before antibiotics; cardiac murmur

Inflammatory/Rheumatologic:

• Adult-onset Still's disease - Quotidian fever pattern, salmon-pink evanescent rash, extreme ferritin (>5x normal), arthritis 3
• Systemic juvenile idiopathic arthritis - Joint involvement, serositis, hepatosplenomegaly

Diagnostic Algorithm

Step 1 (Day 1 - Emergency):

1. Obtain echocardiogram immediately
2. Send CBC, CMP, ESR, CRP, troponin, BNP
3. Blood cultures x2 (before any antibiotics)
4. SARS-CoV-2 PCR and serology
5. Throat culture/rapid strep
6. Urinalysis

Step 2 (If Initial Tests Support KD/MIS-C):

• Ferritin, D-dimer, fibrinogen, procalcitonin
• Viral panel (EBV, adenovirus, enterovirus)
• Liver enzymes, albumin
• Platelet count monitoring (thrombocytosis develops week 2-3)

Step 3 (If Diagnosis Unclear After 48 Hours):

• Repeat echocardiogram if initially normal but clinical suspicion high
• Consider infectious disease consultation
• If inflammatory markers extremely elevated (ESR >240, CRP >25) with negative infectious workup, consider rheumatology consultation 2

Treatment Implications

If KD is confirmed or strongly suspected, treatment must begin immediately:

• IVIG 2 g/kg as single infusion within 10 days of fever onset
• High-dose aspirin 80-100 mg/kg/day divided QID until afebrile 48-72 hours
• Fever typically resolves within 36-48 hours of IVIG

Delaying treatment beyond day 10 of fever increases coronary aneurysm risk from 5% to 20-25% 1.

Key Clinical Pearls

• The vomiting and cough are consistent with KD - GI symptoms occur in 60% of cases; respiratory symptoms from systemic inflammation
• The intermittent nature of symptoms is typical - Features appear sequentially, not simultaneously
• The 3-day duration of hand/foot changes is early - Desquamation comes later (weeks 2-3), but acute erythema/edema occurs now
• Age 16 is unusual but not exclusionary - Maintain high suspicion despite atypical age

Do not wait for all 5 principal features to appear before treating—coronary damage is time-dependent and irreversible.