---
title: "Hand, Foot, and Mouth Disease (HFMD) & Herpangina"
type: clinical-overview
specialty: INF
tags: [hand-foot-mouth-disease, HFMD, herpangina, enterovirus, EV-A71, coxsackievirus-A6, pediatric-infection]
created: 2026-07-15
updated: "2026"
modified: 2026-07-15
---

# Hand, Foot, and Mouth Disease (HFMD) & Herpangina — Clinical Overview

> [!info] Update scope
> 資料更新至 2026-07；整合 *UpToDate* 2026、Saguil et al. 2019 rapid evidence review、Taiwan CDC 2025–2026 guidance，以及 Taiwan EV-A71 vaccine evidence。

## 1. Clinical frame

**Hand, foot, and mouth disease (HFMD)** 是由 **nonpolio enteroviruses** 引起的 acute febrile exanthem，典型組合為：

- **Oral enanthem**：painful vesicles / shallow ulcers。
- **Acral exanthem**：macules、papules 或 vesicles，常見於 palms、soles，也可延伸至 buttocks、arms、legs。
- 多數為 self-limited disease，約 **7–10 days** 內改善。

**Herpangina** 同屬 enterovirus spectrum，但病灶以 **posterior oropharynx** 為主，通常沒有 skin eruption。

| Feature | Typical HFMD | Herpangina | Primary HSV gingivostomatitis |
|---|---|---|---|
| Oral distribution | tongue、buccal mucosa、anterior mouth；可延伸至 soft palate | soft palate、tonsillar pillars、uvula，通常 posterior | diffuse anterior oral cavity、gingiva、lips |
| Skin findings | palms / soles ± buttocks / extremities | absent | perioral vesicles 可有，但無典型 acral exanthem |
| Fever | 常 low-grade | 常 abrupt high fever | 常 high fever、marked malaise |
| Key clue | oral lesions + acral lesions | posterior lesions without rash | painful gingivitis、friable/bleeding gums、diffuse ulcers |

> [!tip] Fast recognition
> 看到 **oral ulcer + palm/sole lesion**，先想 HFMD；看到 **posterior oral ulcer without rash**，先想 herpangina；看到 **diffuse gingivitis + anterior ulcers**，優先考慮 primary HSV gingivostomatitis。

## 2. Virology & epidemiology

- 最常見 pathogens 為 **Coxsackievirus A16 (CV-A16)**、**Enterovirus A71 (EV-A71)** 與 **Coxsackievirus A6 (CV-A6)**；其他 enterovirus serotypes 亦可致病。
- **CV-A6** 與 atypical、widespread、vesiculobullous disease、eczema coxsackium、delayed desquamation / onychomadesis 關聯較強。
- **EV-A71** historically 與 rhombencephalitis、acute flaccid paralysis、autonomic/cardiopulmonary collapse 等 severe disease 關聯最明確；但 **severe enterovirus disease 並非 EV-A71 專屬**。
- Taiwan CDC 2026 surveillance 顯示 community isolates 以 **CV-A6** 為主，其次為 **CV-A4 / CV-A16**；當年 severe cases 亦見 **Enterovirus D68、CV-A4、CV-A16**。
- 主要影響 infants 與 children <5–7 years，但 adolescents、adults、pregnant patients 皆可能感染。
- Temperate climates 常於 summer–early autumn 上升；tropical/subtropical regions 可全年發生。

![[hfmd-uptodate-virology-table-20260715-01.png]]

*Source image: HFMD.pdf, UpToDate Table 1, PDF p.24。表格呈現 enterovirus taxonomy 與常見 clinical syndromes。*

## 3. Transmission & pathogenesis

### Transmission

- fecal–oral contact
- oral–oral / respiratory secretions
- vesicle fluid
- contaminated hands、surfaces 與 fomites

Incubation 通常 **3–5 days**，文獻範圍約 **2–7 days**。第一週 contagiousness 最高；即使症狀改善，virus 仍可由 stool 持續排出。Taiwan CDC 提醒 stool shedding 可達 **8–12 weeks**，因此不能以「完全停止 viral shedding」作為 return-to-school 條件。人類是唯一 reservoir；EV-A71 的 **household transmission rate 高達 52–84%**（Saguil et al. 2019），說明 hand hygiene 與環境清潔在家庭群聚中的重要性。

### Pathogenesis

Virus 先於 oropharyngeal / intestinal mucosa replication，進入 regional lymphoid tissue，經 minor viremia 形成 mucocutaneous disease；若發生 major viremia 與 neurotropism，可能侵犯 CNS、heart 或 lung。

## 4. Clinical presentation

### 4.1 Typical HFMD

- Prodrome 可有 low-grade fever、sore throat、poor appetite、malaise。
- Oral lesions 常先出現：1–5 mm vesicles 很快 rupture，成為 1–10 mm shallow ulcers；疼痛可造成 food/fluid refusal。
- Skin lesions 多為 nonpruritic、painless macules / papules / vesicles，典型 **2–6 mm、周圍有 erythematous halo**，evolve 成 vesicle 後 rupture，留下 painless shallow ulcer 且 **通常不留疤**；常沿 skin lines 呈橢圓形。
- 約 75% 同時有 enanthem 與 exanthem；少數只有 oral 或 skin findings。

![[hfmd-uptodate-classic-oral-skin-findings-20260715-01.jpg]]

*Source images: HFMD.pdf, UpToDate Pictures 1A、1B、2, PDF pp.25–27；典型 oral（tongue + buccal mucosa）與 foot vesicular lesions。*

![[hfmd-afp-classic-palms-soles-oral-2019-20260715-01.jpg]]

*Source images: HFMD2.pdf, Saguil et al. 2019 Figures 1–3, PDF pp.2–3；classic palms、soles 與 oral ulcers。*

### 4.2 Atypical HFMD / CV-A6 phenotype

下列 findings 應提高對 CV-A6-associated atypical HFMD 的懷疑：

- higher fever、more severe systemic symptoms
- widespread vesicles、bullae、erosions、eschar
- perioral、trunk、neck、extremity involvement，超出 classic acral distribution
- **eczema coxsackium**：lesions 聚集在 atopic dermatitis、skin injury 或其他 barrier disruption 處
- convalescent palmar/plantar desquamation（約 1–3 weeks）
- **Beau lines / onychomadesis**（常於 3–8 weeks，部分資料描述 1–2 months）

![[hfmd-uptodate-generalized-spectrum-20260715-01.jpg]]

*Source image: HFMD.pdf, UpToDate Picture 3, PDF p.28；generalized HFMD spectrum。*

![[hfmd-uptodate-cva6-child-onychomadesis-20260715-01.jpg]]

*Source image: HFMD.pdf, UpToDate Picture 4, PDF p.29；CV-A6-associated extensive lesions 與 delayed onychomadesis。*

![[hfmd-uptodate-eczema-coxsackium-20260715-01.jpg]]

*Source image: HFMD.pdf, UpToDate Picture 5, PDF p.30；eczema coxsackium。*

![[hfmd-uptodate-atypical-cva6-adult-20260715-01.jpg]]

*Source image: HFMD.pdf, UpToDate Picture 6, PDF p.31；adult atypical CV-A6 HFMD。*

### 4.3 Herpangina

- abrupt fever，常達 38.9–40°C
- sore throat、odynophagia、poor intake
- 通常 <10 個 painful papulovesicular / ulcerative lesions
- 位於 anterior tonsillar pillars、soft palate、tonsils、uvula
- **absence of skin lesions** 是與 HFMD 區分的核心
- fever 常約 2 days 改善，oral lesions 約 5–6 days 消退

![[hfmd-uptodate-herpangina-20260715-01.jpg]]

*Source image: HFMD.pdf, UpToDate Picture 7, PDF p.32；posterior oropharyngeal lesions of herpangina。*

## 5. Severe disease & complications

### Common / usually limited

- dehydration due to odynophagia
- secondary bacterial infection of disrupted skin（uncommon）
- late desquamation、Beau lines、onychomadesis

### Neurologic / cardiopulmonary complications

- aseptic meningitis
- encephalitis / rhombencephalitis
- acute flaccid paralysis
- autonomic dysfunction、tachycardia、hypertension
- myocarditis、heart failure
- neurogenic pulmonary edema / pulmonary hemorrhage

> [!danger] Taiwan CDC severe warning signs
> 出現 **lethargy / altered consciousness / poor activity、limb weakness or paralysis、myoclonus、persistent vomiting、tachypnea 或 tachycardia**，應立即轉送 acute care 評估。Young age、persistent fever ≥3 days、vomiting、lethargy 與 EV-A71 infection 亦與 severe disease risk 增加有關。

> [!warning] Do not anchor on EV-A71
> EV-A71 是經典 high-risk serotype，但 current Taiwan surveillance 顯示其他 enteroviruses 也可造成 severe disease；triage 應以 clinical red flags 為主，不應等 serotype result。

## 6. Diagnosis & workup

### 6.1 Clinical diagnosis

典型 HFMD / herpangina 通常不需要 laboratory confirmation。Diagnosis 依 lesion morphology、distribution、age、season 與 exposure history。

### 6.2 When to test

考慮 sampling / NAAT 的情境：

- atypical or severe disease
- CNS / cardiopulmonary complication
- immunocompromised host
- outbreak investigation / public-health need
- eczema coxsackium 與 eczema herpeticum 無法可靠區分
- differential 包含 varicella、HSV、mpox 等需特異治療或 isolation 的疾病

### 6.3 Specimen interpretation

- **Vesicle fluid NAAT** 最能將 skin lesion 與 enterovirus 建立 causal link。
- 有 meningitis / encephalitis 時送 **CSF NAAT**；但 EV-A71 CNS disease 的 CSF viral yield 可能不高，仍需 throat / stool 等 paired specimens 與 clinical interpretation。
- Throat / stool NAAT 可提高 detection，但可能代表 prolonged shedding，不能單獨證明當下 syndrome 的 cause。

### 6.4 Differential diagnosis

| Disease | Distinguishing clues |
|---|---|
| Aphthous ulcers | isolated recurrent oral ulcers；no fever、no acral exanthem |
| Primary HSV gingivostomatitis | diffuse painful gingivitis、friable/bleeding gums、anterior oral/labial lesions |
| Eczema herpeticum | monomorphic punched-out erosions、pain、systemic toxicity；需 urgent HSV PCR 與 empiric antiviral consideration |
| Varicella | lesions in multiple stages，trunk-predominant，通常 pruritic |
| Erythema multiforme major | target lesions，often acral/symmetric；prominent mucosal involvement 可見 |
| Mpox | deep-seated / umbilicated lesions、lymphadenopathy、epidemiologic risk |
| Papular urticaria / contact dermatitis | pruritus 與 exposure pattern；通常無 oral enanthem |
| Stevens–Johnson syndrome / toxic epidermal necrolysis | medication exposure、prominent mucosal disease、skin pain / detachment、systemic illness |

![[hfmd-afp-differential-table-2019-20260715-01.png]]

*Source image: HFMD2.pdf, Saguil et al. 2019 Table 1, PDF pp.4–5。此表適合比較 morphology / differential；其 treatment 欄為 2019 snapshot，部分內容已過時，實際治療須依 current disease-specific guidance。*

## 7. Management

### 7.1 Uncomplicated disease

Treatment 為 **supportive care**：

- encourage frequent cool fluids；依 hydration status 調整 oral / IV rehydration
- acetaminophen 或 ibuprofen 依 age、weight、contraindications 與 current formulary 用於 pain / fever
- soft foods；避免 acidic / spicy foods 加重 oral pain
- skin lesions 保持清潔乾燥，避免刺破 vesicles

> [!warning] Avoid
> - **Topical oral lidocaine、diphenhydramine mixtures 或其他 topical anesthetics**：children 缺乏明確 benefit，且可能造成 systemic toxicity / aspiration risk。
> - **Acyclovir**：enteroviruses 缺乏使 acyclovir 活化所需的 thymidine kinase，無 controlled evidence 支持用於 HFMD。
> - **Antibiotics**：除非另有 bacterial infection evidence。
> - Dehydrated child 使用 NSAID 前，先 correction of volume depletion 並評估 kidney risk。

### 7.2 Admit / urgent referral when

- inability to maintain hydration、oliguria 或 hemodynamic compromise
- neurologic warning signs / altered mental status / weakness / myoclonus
- tachypnea、tachycardia 或 suspected myocarditis / pulmonary edema
- severe pain 無法 outpatient control
- immunocompromised host with extensive disease
- eczema coxsackium 與 eczema herpeticum 無法區分，且需要 urgent HSV-directed management

Severe enterovirus CNS / cardiopulmonary disease 的 critical care、IVIG 或其他 adjunctive therapy 應依 Taiwan severe-enterovirus protocol 與 specialist assessment；**不是 uncomplicated HFMD 的 routine therapy**。

![[hfmd-afp-key-recommendations-2019-20260715-01.png]]

*Source image: HFMD2.pdf, Saguil et al. 2019 SORT recommendations, PDF p.2。核心 supportive-care principles 仍適用；vaccine statement 已因 Taiwan 2023 EV-A71 vaccines 上市而過時。*

## 8. Infection control & return to childcare/school

### Household / clinic

- soap-and-water hand hygiene，尤其 diaper change、toileting、feeding 前後
- 不共用 cups、utensils、towels；清潔 toys、high-touch surfaces 與 diaper areas
- Alcohol 對 enteroviruses 的 inactivation 效果有限；環境消毒優先依 Taiwan CDC 使用 chlorine-based disinfectant
- 一般環境可用 **500 ppm available chlorine**；Taiwan CDC example 為 10 L water + 100 mL household chlorine bleach，實際仍需依產品原始 concentration 換算
- Healthcare settings 採 **Standard + Contact Precautions**；依 local policy 加強 droplet / outbreak control

### Childcare / school

- Child 有 fever、無法正常參與活動、open/draining blisters 或 uncontrolled drooling 時留在家中。
- 症狀改善後可依 local public-health / childcare policy return；排毒可持續數週，單純延長 exclusion 無法完全阻斷 transmission。
- Taiwan CDC 所列 childcare closure framework 會依 EV-A71 epidemic activity、同班 cases 與 local government rules 調整；常見 default closure period 為 **7 days**，但須以所在地衛生主管機關最新公告為準。

## 9. EV-A71 vaccine in Taiwan

Taiwan 自 2023 年起有兩種 **whole-virus inactivated EV-A71 vaccines** 上市：

- 適用年齡為 **2 months to <6 years**，由 physician assessment 後自費接種。
- Protection 針對 **EV-A71**；目前沒有證據顯示可 cross-protect CV-A16、CV-A6、Enterovirus D68 等其他 serotypes，因此接種後仍可能得到 HFMD。
- Prior dose / component 曾 severe allergic reaction 者 contraindicated。
- Acute serious febrile illness / infection 時先 defer，待病情穩定後接種。
- 不同 product 的 primary series / booster schedule 可能不同，應依 product label 與 Taiwan CDC current recommendation。

Phase 3 evidence 顯示 inactivated EV-A71 vaccine 可預防 EV-A71-associated HFMD；但不能把此 efficacy 外推至 all-cause HFMD。

## 10. Prognosis & follow-up

- Typical HFMD 多在 7–10 days 完全改善。
- Skin lesions 通常不留疤；extensive bullous / erosive lesions 需追蹤 secondary infection。
- Palmar/plantar desquamation 可於 1–3 weeks 後出現。
- Beau lines / onychomadesis 常於 3–8 weeks 後出現，通常 nail matrix 會自行恢復；若持續疼痛、periungual inflammation 或 regrowth abnormality，再轉 Dermatology。
- Safety-net 應明確交代 hydration、urine output、mental status、limb strength、breathing 與 heart rate changes。

## 11. Clinical pearls

1. HFMD diagnosis 重點是 **oral + acral distribution**，不是每個 case 都有完整 triad。
2. CV-A6 可 mimick varicella、eczema herpeticum、erythema multiforme 或 Stevens–Johnson syndrome。
3. Stool / throat NAAT positive 可能只是 prolonged shedding；specimen site 與 phenotype 必須一起解讀。
4. Myoclonus、limb weakness、persistent vomiting、tachypnea / tachycardia 是 severe warning signs，不要等 EV-A71 typing。
5. Onychomadesis 是 well-described delayed sequela，通常 self-limited，可先 reassurance。
6. EV-A71 vaccine 已在 Taiwan 可用，但只處理 EV-A71 risk，不能取代 hand hygiene 與 outbreak control。

## Related notes

- [[Infectious disease(INF)/cns-infections/viral-encephalitis|Viral Encephalitis]] — enterovirus encephalitis / rhombencephalitis
- [[Infectious disease(INF)/cns-infections/aseptic-meningitis|Aseptic Meningitis]] — enterovirus meningitis 與 CSF evaluation
- [[Dermatology(DERM)/drug-eruptions/drug-eruptions_overview|Drug Eruptions]] — erythema multiforme / SJS-TEN differential
- [[Infectious disease(INF)/skin-soft-tissue-infections/skin-soft-tissue-infections_overview|Skin & Soft Tissue Infections]] — secondary bacterial infection assessment

## Key references

1. Olarte L, Edwards MS. **Hand, foot, and mouth disease and herpangina.** *UpToDate*. Literature review current through Jun 2026; topic last updated Jul 8, 2025. [Topic](https://www.uptodate.com/contents/hand-foot-and-mouth-disease-and-herpangina)
2. Saguil A, Kane SF, Lauters R, Mercado MG. **Hand-Foot-and-Mouth Disease: Rapid Evidence Review.** *Am Fam Physician.* 2019;100(7):408-414. PMID: 31573162. [Full text](https://www.aafp.org/pubs/afp/issues/2019/1001/p408.html)
3. Taiwan Centers for Disease Control. **Enterovirus infection with severe complications / HFMD Q&A.** Updated Jun 20, 2025. [Taiwan CDC](https://www.cdc.gov.tw/Category/QAPage/uWGc1UXjKbX7uC1uTG5_2Q)
4. Taiwan Centers for Disease Control. **EV-A71 vaccine.** [Taiwan CDC](https://www.cdc.gov.tw/Category/Page/u87VWWvbc8dH6BcgAguctw)
5. Taiwan Centers for Disease Control. **2026 enterovirus surveillance and severe-case warning signs.** Apr 21, 2026. [Taiwan CDC](https://www.cdc.gov.tw/Bulletin/Detail/TwK1wW9dD65xtZ6pMEJ79Q?typeid=9)
6. Nguyễn TT, et al. **Efficacy, safety, and immunogenicity of an inactivated, adjuvanted enterovirus 71 vaccine in infants and children: a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.** *Lancet.* 2022;399(10336):1708-1717. PMID: 35427481. DOI: 10.1016/S0140-6736(22)00313-0.
7. Ho M, et al. **An epidemic of enterovirus 71 infection in Taiwan.** *N Engl J Med.* 1999;341(13):929-935. PMID: 10498487. DOI: 10.1056/NEJM199909233411301.