HFMD - Hand foot mouth disease, Overview

HFMD is a common, self-limiting viral illness primarily affecting children under 5 years. The infection usually involves the hands, feet, mouth, and sometimes, even the genitals and buttocks

1. By: Uparna Sayuri Heenatigala Group 10, Sem 12 TSMU Hand-Foot-and-Mouth Disease (HFMD)

2. Introduction HFMD is a common, self-limiting viral illness primarily affecting children under 5 years. The infection usually involves the hands, feet, mouth, and sometimes, even the genitals and buttocks Epidemiology: Age Group: Predominantly in children under 5 years. Seasonality: Peaks in summer and early autumn. Transmission: Highly contagious; spreads via direct contact with nasal secretions, saliva, blister fluid, stool, or respiratory droplets .

3. Causative Agents Primary Viruses: Coxsackievirus A16 : Most common cause . Enterovirus 71 (EV-A71) : Associated with more severe cases. Other Enteroviruses: Coxsackievirus A6, A10, A5, A9, B1, B3 . Family: Picornaviridae . Small, non-enveloped, icosahedral viruses. Single-stranded, positive-sense RNA genome. Genera: Enterovirus : Includes poliovirus, coxsackieviruses, echoviruses. Rhinovirus : Common cold viruses. Hepatovirus : Hepatitis A virus. Transmission: Fecal -oral route, respiratory droplets, or contact with contaminated surfaces. Their small size and acid stability allow them to survive in the gastrointestinal tract and spread via fecal -oral transmission .

4. Pathophysiology Entry Points: Virus enters through the oral or nasal mucosa. Replication: Initial replication in the oropharyngeal and intestinal mucosa. Dissemination: Spreads to regional lymph nodes, leading to viremia. This can be spread to multiple organs, including the central nervous system, heart, liver, and skin. Target Organs: Skin and mucous membranes, leading to characteristic lesions .

5. Clinical Course Incubation Period: 3–6 days. Prodromal Symptoms: Low-grade fever, Malaise, Anorexia, Sore throat. Progression: Development of painful oral ulcers and appearance of vesicular rash on hands, feet, and sometimes buttocks . Oral Lesions (Enanthem) Vesicles are: Surrounded by a thin halo of erythema They eventually rupture , forming: Superficial ulcers w ith a grey-yellow base and an erythematous rim Common sites of oral lesions: Buccal mucosa , Tongue , soft palate Can cause drooling, irritability or crying with eating and difficulty in eating and drinking, leading to dehydration.

6. Skin Lesions Appearance: The exanthem can be macular, papular , or vesicular. (may blister) Lesion characteristics: Size: About 2 mm to 6 mm Non-pruritic Typically not painful Tend to rupture, resulting in: Painless, shallow ulcers that do not leave a scar Distribution: Palms of hands. Soles of feet. Buttocks and sometimes legs and arms. Duration: Lesions usually resolve without scarring in 7–10 days .

7. Atypical Features and Neurological Involvement HFMD can also present with atypical features , such as: Concomitant aseptic meningitis (Irritability, Poor feeding, Lethargy or excessive sleepiness and High-pitched cry) Caused by Enterovirus 71 (EV-A71) or Coxsackievirus A9 and A16 Usually occurs within a few days of the onset of typical HFMD symptoms (rash, oral ulcers, fever) Can precede, coincide with, or follow the cutaneous and oral manifestations Enterovirus infections that cause HFMD are notorious for central nervous system involvement , which may result in: Encephalitis Polio-like syndrome Acute transverse myelitis Guillain-Barré syndrome Benign intracranial hypertension Acute cerebellar ataxia Common: Dehydration due to painful oral lesions. Rare: Viral meningitis, Encephalitis, Nail loss (onychomadesis) Severe Cases: More likely with EV-A71 infections. Neurological complications may require hospitalization.

8. HFMD and Viral Encephalitis The virus first replicates in the oropharynx and gastrointestinal tract , leading to viremia. In neurotropic strains (especially EV-A71), the virus can: Cross the blood-brain barrier Enter the central nervous system Infect brainstem and spinal cord neurons Encephalitic Features: Altered mental status (confusion, stupor, or coma) Seizures (focal or generalized) Myoclonus (especially facial or limb twitches) Cranial nerve palsies Ataxia , tremors Treatment Supportive care in ICU settings : Maintain airway, breathing, and circulation Manage seizures and intracranial pressure IVIG may be used in severe cases (evidence limited but suggested in some studies) No specific antiviral therapy exists Close neurologic monitoring is essential

9. HFMD and Chicken Pox

10. Condition Rash Distribution Rash Characteristics Oral Lesions Systemic Symptoms Herpes Simplex Virus (HSV) Face, lips Painful vesicles , clustered Common : painful oral lesions Fever, oral pain Molluscum Contagiosum Face, trunk, limbs, genital area Papules with central umbilication None Usually none Scarlet Fever Neck, chest, spreads to body Sandpaper-like , red rash Rare, mild enanthem High fever , sore throat Erythema Infectiosum (Fifth Disease) Face (slapped-cheek) , trunk, limbs Lacy red rash None Mild fever , headache Bullous Impetigo Face, neck, extremities Large, fluid-filled blisters that crust None Fever, malaise Toxic Shock Syndrome (TSS) Widespread , can lead to peeling Erythematous , desquamation later None High fever , hypotension Kawasaki Disease Trunk, limbs, extremities Polymorphous rash, erythematous None (strawberry tongue) High fever , conjunctivitis Measles (Rubeola) Face, neck, trunk Morbilliform , maculopapular Koplik spots in mouth Fever, cough, conjunctivitis Rubella (German Measles) Face, trunk, limbs Maculopapular , pink rash None Mild fever , lymphadenopathy Viral Exanthems Trunk, face, limbs Maculopapular , non-vesicular Rare or absent Fever, sore throat Differential diagnosis

11. Treatment Clinical Course and Resolution HFMD is a mild clinical syndrome that generally resolves within 7 to 10 days . Treatment is primarily supportive . Symptomatic Management Pain and Fever : Can be managed with NSAIDs (e.g., ibuprofen) and acetaminophen . Hydration : Ensuring the patient remains well-hydrated is crucial. Topical Pain Relief : A mixture of ibuprofen and diphenhydramine can be used for gargling to coat the ulcers and ease pain. Steroid Use and Risks Steroids : Found to increase the risk of severe HFMD and are not recommended for treatment. No Specific Antiviral Therapy: Antibiotics are ineffective as HFMD is viral . Hospitalization: Necessary in cases of severe dehydration or neurological complications.

12. Prognosis The prognosis for most patients with HFMD is excellent. Most patients recover within a few weeks without any residual sequelae. Acute illness usually lasts 10 to 14 days, and the infection rarely recurs or persists. However, some patients with HFMD may develop serious complications, which include the following: Persistent stomatitis is associated with painful ulcers. The pain can be severe enough to limit food intake, and dehydration can result, especially in young children. Aseptic meningitis can occur, but this is more common with enterovirus 71. This particular virus is associated with a higher neurological involvement rate than coxsackievirus. The individual may develop acute cerebellar ataxia, polio-like syndrome, encephalitis, benign intracranial hypertension, and Guillain-Barre syndrome. The virus is believed to induce damage to the gray matter, resulting in motor dysfunction. Coxsackievirus can rarely cause interstitial pneumonia, myocarditis, pancreatitis, and pulmonary edema. Some studies indicate that coxsackievirus infections may also be associated with spontaneous abortions.

13. References Enterovirus-Associated Hand-Foot and Mouth Disease and Neurological Complications in Japan and the Rest of the World. Gabriel Gonzalez   1,2 ,  Michael J Carr   3,4 ,  Masaaki Kobayashi   5 ,  Nozomu Hanaoka   6 ,  Tsuguto Fujimoto   6,* Clinical manifestations of CNS infections caused by enterovirus type 71 Korean J Pediatr , 54 (1) (2011), pp. 11-16. B.P. Zhou, C.R. Li Enterovirus 71 hand mouth foot disease People’s Medical Publishing House, Beijing (2009), pp. 202-204 K. Liu, Y.X. Ma, C.B. Zhang, Y.P. Chen, X.J. Ye, G.H. Bai,  et al. Neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease:clinical features, MRI findings and follow-up study Natl Med J China, 92 (25) (2012), pp. 1742-1746 WHO.  W.H.O. a Guide to Clinical Management and Public Health Response for Hand, Foot and Mouth Disease (HFMD) ; WHO Regional Office for the Western Pacific: Manila, Philippines, 2011. [ Google Scholar ]

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