Initial Presentation of Hand, Foot, and Mouth Disease in Toddlers

Initial Symptoms

Fever is usually the first symptom, typically low-grade but can be higher than 102.2°F (39°C), often accompanied by malaise, general discomfort, sore throat, and irritability in toddlers, according to the American Academy of Pediatrics 1
Respiratory symptoms such as cough and rhinitis may accompany the classic presentation in some cases, especially in younger children 1
Gastrointestinal symptoms including nausea, vomiting, and diarrhea are occasionally reported in toddlers with HFMD 1

Unlike Kawasaki disease, HFMD presents with vesicular lesions rather than diffuse erythema, as noted by the American Heart Association 2 and the American College of Cardiology 3
Unlike chickenpox, HFMD vesicles are typically concentrated on hands, feet, and mouth rather than being widely distributed, according to the Infectious Diseases Society of America 4
HFMD does not typically present with the high, persistent fever seen in more serious conditions like Kawasaki disease, as distinguished by the American Heart Association 2 and the American College of Cardiology 3

The exanthem typically begins as small, pink macules that evolve to vesicular lesions, with a highly characteristic distribution on palms and soles, according to the MMWR Recommendations and Reports 5
A rash on the palms and soles is not unique to HFMD and can occur in other conditions, including drug hypersensitivity reactions, infective endocarditis, Streptobacillus moniliformis infection, and Ehrlichiosis, as noted by the MMWR Recommendations and Reports 5

Syphilis (Treponema pallidum) and Meningococcal infection (Neisseria meningitidis) are among the conditions that can present with a rash on the palms and soles, similar to HFMD, as reported by the MMWR Recommendations and Reports 6
Rocky Mountain spotted fever, although typically presenting with a petechial rash, can also be considered in the differential diagnosis of HFMD, according to the MMWR Recommendations and Reports 6

Chemotherapy-induced hand-foot syndrome presents with dysesthesia, burning pain, and hyperkeratosis rather than discrete vesicles, according to the European Society for Medical Oncology 7