What is the most likely diagnosis for a patient presenting with fever, sore throat, and papular/vesicular lesions on the inner cheek?

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Last updated: February 23, 2026View editorial policy

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Diagnosis: Hand, Foot, and Mouth Disease (HFMD)

The most likely diagnosis is hand, foot, and mouth disease (HFMD), a viral exanthem caused primarily by Coxsackievirus A16, Coxsackievirus A6, or Enterovirus 71, characterized by fever, sore throat, and papular/vesicular lesions on the oral mucosa (inner cheeks, palate, pharynx). 1, 2

Key Diagnostic Features

Classic Presentation

  • Fever accompanied by painful papules, vesicles, or ulcerations inside the mouth (buccal mucosa, palate, pharynx) is the hallmark of HFMD 1, 3
  • Oral lesions typically appear first, often before skin manifestations develop on the hands, feet, or buttocks 3
  • The enanthem involves vesiculation and ulceration of the mouth, palate, and pharynx, causing significant sore throat and odynophagia 1

Atypical Presentations (Coxsackievirus A6)

  • Since 2008–2011, Coxsackievirus A6 has caused more extensive disease with widespread vesiculobullous eruptions extending beyond the classic hand-foot-mouth distribution 4, 2
  • Peri-oral rash is strongly associated with CV-A6 (P < 0.001) 2
  • Generalized exanthema involving 5 or more anatomical sites (hands, feet, mouth, buttocks, legs, arms, trunk) occurs in 41.5% of confirmed cases 2
  • High fever and vesiculobullous eruptions on the calves and backs of hands characterize the atypical CV-A6 variant 4

Differentiating HFMD from Other Causes

Why Not Herpes Simplex Virus (HSV)?

  • HSV-1 causes gingivostomatitis with gingival inflammation and bleeding, not isolated papules on the buccal mucosa 5
  • HSV labialis primarily affects the lips and perioral skin, not intraoral surfaces 5
  • HSV does not typically produce the hand-foot distribution seen in HFMD 3

Why Not Group A Streptococcus (Scarlet Fever)?

  • Scarlet fever presents with a sandpaper-like rash on the trunk and extremities, not vesicular oral lesions 6
  • The pharyngitis in scarlet fever shows tonsillopharyngeal erythema with exudates and palatal petechiae, not discrete papules or vesicles on the buccal mucosa 6
  • Microbiological confirmation (RADT or throat culture) is required to diagnose GAS pharyngitis; clinical features alone are insufficient 7, 8

Why Not Other Viral Pharyngitis?

  • Adenovirus, rhinovirus, and respiratory syncytial virus cause pharyngitis with prominent upper respiratory symptoms (cough, rhinorrhea, hoarseness, conjunctivitis) 7, 9
  • These viruses do not produce the characteristic vesicular oral lesions seen in HFMD 7

Diagnostic Confirmation

  • Clinical diagnosis is usually sufficient when the classic triad of fever, oral vesicles/ulcers, and hand-foot lesions is present 1, 3
  • PCR of vesicular swabs or stool samples can confirm enterovirus infection and identify the specific serotype (CV-A6, CV-A16, EV-71) 4, 2
  • Laboratory testing is not routinely necessary unless the presentation is atypical or severe neurological complications are suspected 1

Management

  • Treatment is palliative only: analgesics (acetaminophen or ibuprofen, avoiding aspirin in children), adequate hydration, topical oral anesthetics (lidocaine gel), and soft diet 3, 7
  • Antibiotics are not indicated for HFMD; this is a self-limiting viral illness 7
  • Symptoms typically resolve within 7–10 days without complications 3, 4
  • Onychomadesis (nail shedding) may occur 4–6 weeks after infection, particularly with CV-A6 4, 1

Common Pitfalls

  • Do not mistake HFMD for bacterial pharyngitis and prescribe unnecessary antibiotics; the presence of oral vesicles/papules strongly favors a viral etiology 7
  • Do not overlook Enterovirus 71 in endemic areas (Asia), which can cause severe neurological complications including encephalitis, aseptic meningitis, and acute flaccid paralysis 1, 5
  • Recognize that CV-A6 can cause extensive disease that may initially be mistaken for varicella, eczema herpeticum, or Stevens-Johnson syndrome 4, 1
  • Transmission occurs via fecal-oral route and respiratory droplets; household contacts (including adults) are at risk 1

References

Research

Update on hand-foot-and-mouth disease.

Clinics in dermatology, 2015

Research

Hand, foot, and mouth disease: a viral disease of importance to dentists.

Journal of the American Dental Association (1939), 1975

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Scarlet Fever Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Differentiating Viral and Bacterial Pharyngitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Guideline Summary for Diagnosis and Management of Group A Streptococcal Pharyngitis in Children

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Causes, diagnosis, and treatment of pharyngitis.

Comprehensive therapy, 1990

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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