What is the diagnosis for a patient presenting with fever and subsequent lip rashes?

Kawasaki Disease

The most likely diagnosis for a patient presenting with fever followed by lip rashes is Kawasaki disease, which requires immediate recognition and treatment to prevent coronary artery complications. 1

Diagnostic Criteria

The diagnosis of Kawasaki disease is established when fever persists for at least 5 days plus 4 of the following 5 principal clinical features: 1

• Changes in lips and oral cavity: Erythema, lip cracking, fissuring, peeling, bleeding of the lips, and "strawberry tongue" with prominent fungiform papillae 1
• Polymorphous exanthem: Nonspecific diffuse maculopapular eruption, urticarial exanthem, or scarlatiniform rash involving trunk and extremities with perineal accentuation 1
• Bilateral bulbar conjunctival injection without exudate 1
• Changes in extremities: Acute erythema of palms/soles with edema of hands/feet, followed by periungual peeling in weeks 2-3 1
• Cervical lymphadenopathy (≥1.5 cm diameter), usually unilateral 1

Critical Timing and Presentation

The fever in Kawasaki disease is characteristically high-spiking (typically 39-40°C or 102-104°F) and remittent, persisting for a mean of 11 days without treatment but resolving within 2 days with appropriate therapy. 1 The clinical features do not all appear simultaneously—watchful waiting is often necessary before the full diagnostic picture emerges. 1

The diagnosis can be made on day 4 of illness if 4 principal criteria are present, or earlier if coronary artery disease is detected by echocardiography. 1

Key Distinguishing Features for Lip Involvement

The lip changes in Kawasaki disease are distinctive and include erythema, dryness, fissuring, peeling, cracking, and bleeding—not simply a rash. 1 The oral cavity shows diffuse erythema of the oropharyngeal mucosae, but notably oral ulcerations and pharyngeal exudates are NOT seen, which helps distinguish this from other conditions. 1

Critical Differential Diagnoses to Exclude

The American Heart Association guidelines emphasize excluding other diseases with similar findings: 1

• Viral infections (measles, adenovirus, enterovirus, Epstein-Barr virus)
• Scarlet fever and toxic shock syndrome
• Stevens-Johnson syndrome
• Drug hypersensitivity reactions
• Staphylococcal scalded skin syndrome

Herpes Simplex Labialis Consideration

While herpes simplex virus can cause labial lesions (cold sores), this typically presents as grouped vesicles or ulcers on an erythematous base rather than the diffuse erythema, cracking, and fissuring seen in Kawasaki disease. 2, 3 In children with HSV encephalitis, labial herpes may be noted as a marker of primary infection, but this occurs in the context of neurological symptoms rather than the multisystem presentation of Kawasaki disease. 1

Immediate Management Implications

Cardiovascular manifestations are the leading cause of long-term morbidity and mortality in Kawasaki disease. 1 During the acute phase, the pericardium, myocardium, endocardium, valves, and coronary arteries may all be involved. 1 Physical examination often reveals tachycardia, a hyperdynamic precordium, gallop rhythm, and flow murmurs. 1

The priority is prompt recognition and initiation of treatment with intravenous immunoglobulin and aspirin to reduce the risk of coronary artery aneurysms, which develop in approximately 25% of untreated patients. 1

Common Pitfalls to Avoid

• Do not wait for all 5 principal features to appear simultaneously—they evolve over time and watchful observation may be needed. 1
• Do not dismiss the diagnosis based on incomplete criteria early in the illness—if coronary involvement is detected, only 4 criteria are needed. 1
• Do not confuse the lip changes with simple herpes labialis—Kawasaki disease causes diffuse erythema, cracking, and fissuring without the grouped vesicles characteristic of HSV. 1, 2