Clinical Presentation
Incubation: 10-14 days
Contagious: 4 days before to 4 days after rash onset
Prodrome (2-3 days before rash)
High fever (up to 40°C/104°F), malaise, anorexia, followed by the classic triad:
- Cough - harsh, barking
- Coryza - profuse rhinorrhea
- Conjunctivitis - bilateral, non-purulent
🔍 PATHOGNOMONIC SIGN: Koplik spots - Small white spots with red halos on buccal mucosa opposite molars. Appear 2-3 days before rash, pathognomonic for measles.
Rash Evolution
Maculopapular, erythematous rash:
- Day 1: Starts at hairline/forehead, behind ears
- Day 2: Spreads to face, neck, upper trunk
- Day 3: Covers trunk and extends to extremities
- Becomes confluent on face and upper body
- Fades in same order (3-4 days), leaves brownish discoloration
- Fine desquamation follows
Diagnosis
Clinical Criteria
Fever ≥38.3°C (101°F) + generalized maculopapular rash ≥3 days + at least one: cough, coryza, or conjunctivitis
Laboratory Confirmation
| Test |
Details |
| Measles IgM |
Most reliable 3-28 days after rash onset. Preferred test. |
| RT-PCR |
Nasopharyngeal swab, throat swab, or urine. Detects measles RNA. |
| IgG seroconversion |
4-fold rise between acute and convalescent sera |
| Viral culture |
Less commonly used, requires specialized lab |
Complications
⚠️ Common Complications:
- Otitis media (7-9%)
- Pneumonia (1-6%): Viral or bacterial superinfection
- Diarrhea (8%)
- Encephalitis (1:1,000): Acute, can be fatal
- SSPE: Subacute sclerosing panencephalitis years later (rare, 7-11 years post-infection)
Management
Supportive Care
- Antipyretics: Acetaminophen 15 mg/kg q4-6h or Ibuprofen 10 mg/kg q6-8h
- Adequate hydration and nutritional support
- Respiratory support if needed
- Antibiotics ONLY for bacterial superinfections
💊 Vitamin A Supplementation (WHO/AAP Recommendation):
All hospitalized children and children 6 months-2 years:
• ≥1 year: 200,000 IU PO
• 6-11 months: 100,000 IU PO
• Repeat dose next day and at 4 weeks if vitamin A deficiency suspected
Reduces mortality and complications, especially in malnourished children
Isolation
Airborne + Contact precautions. Exclude from school/daycare for 4 days after rash onset.
Post-Exposure Prophylaxis
- MMR vaccine within 72 hours: For individuals ≥6 months without immunity
- Immunoglobulin (IG) within 6 days: 0.25 mL/kg (immunocompetent) or 0.5 mL/kg (immunocompromised) IM for high-risk: infants <12 months, pregnant women, immunocompromised
Prevention
Vaccination
- MMR vaccine schedule: Dose 1 at 12-15 months, Dose 2 at 4-6 years
- Efficacy: 93% after 1 dose, 97% after 2 doses
- Outbreak control: Vaccinate susceptible contacts within 72 hours
📚 Evidence Base: CDC Measles Clinical Overview 2024, AAP Red Book 2024-2027, WHO Guidelines.
2025 US Outbreak Data: 1,408 confirmed cases (as of August 2025), 92% unvaccinated or unknown vaccination status, 13% hospitalization rate, 3 deaths. 35 outbreaks reported.
Clinical Presentation
Incubation: 14-21 days (average 16-18 days)
Contagious: 7 days before to 7 days after rash onset
Prodrome
Mild or absent in children. In adults/adolescents:
- Low-grade fever (usually <39°C)
- Malaise, headache
- Lymphadenopathy: Post-auricular, suboccipital, posterior cervical (appears 5-10 days before rash)
- Arthralgia/arthritis (common in adult women)
🔍 PATHOGNOMONIC SIGN: Forchheimer spots - Petechiae on soft palate appearing before rash (present in ~20% of cases)
Rash
Pink-red, fine maculopapular rash:
- Starts on face, spreads to trunk and extremities within 24 hours
- Discrete lesions (unlike measles' confluent pattern)
- Less intense than measles
- Fades by day 3
- No desquamation
Diagnosis
Clinical diagnosis difficult - mild symptoms, non-specific rash. Laboratory confirmation essential.
| Test |
Details |
| Rubella IgM |
Positive within 4 days of rash, peaks 7-10 days, lasts 4-12 weeks |
| RT-PCR |
Nasopharyngeal or throat swab for rubella RNA |
| IgG seroconversion |
4-fold rise between acute and convalescent sera |
Complications
⚠️ Complications:
- Arthralgia/Arthritis (70% adult women): Symmetric, affects fingers, wrists, knees. Duration 1-3 weeks, can persist months
- Thrombocytopenia (1:3,000)
- Encephalitis (1:5,000-6,000)
- Congenital Rubella Syndrome (CRS): Most devastating complication
🤰 Congenital Rubella Syndrome (CRS):
Maternal infection in first trimester:
• Classic triad: Cataracts, cardiac defects (PDA, pulmonary stenosis), deafness
• Additional: Microcephaly, intellectual disability, hepatosplenomegaly, thrombocytopenia, "blueberry muffin" rash
• Risk decreases with gestational age at infection
Management
Supportive Care
- No specific antiviral therapy available
- Antipyretics for fever: Acetaminophen or ibuprofen
- NSAIDs for arthralgia in adults
- Hydration and rest
Isolation
Droplet precautions. Exclude from school/daycare for 7 days after rash onset.
Pregnancy Management
- Urgent serologic testing if pregnant woman exposed
- Counsel on CRS risks if acute infection confirmed
- No proven therapy to prevent fetal infection
- Infants with CRS: Shed virus for ≥1 year - strict contact precautions
Prevention
- MMR vaccine: Dose 1 at 12-15 months, Dose 2 at 4-6 years (97% protection)
- Preconception: Screen women of childbearing age. Vaccinate if non-immune (avoid pregnancy 28 days post-vaccine)
- Post-exposure: MMR does NOT prevent rubella after exposure but provides future protection
📚 Evidence Base: CDC 2024, AAP Red Book 2024-2027.
Status: Eliminated from Americas since 2015, but importation risk remains. Essential to maintain high vaccination coverage.
Clinical Presentation
Incubation: 2-5 days
Contagious: Until 24 hours after antibiotic therapy initiated
Etiology: Streptococcus pyogenes (Group A Strep) producing pyrogenic exotoxins
Prodrome
- Sudden onset high fever (39-40°C)
- Severe sore throat
- Headache, chills
- Vomiting, abdominal pain (especially in children)
🔍 PATHOGNOMONIC SIGNS:
1. Strawberry Tongue:
• Days 1-2: White coating with red papillae protruding ("white strawberry")
• Days 4-5: White coating sheds, bright red tongue with prominent papillae ("red strawberry")
2. Pastia Lines: Petechial lines in skin folds (antecubital fossae, axillae, groin)
Rash
Characteristic "sandpaper" exanthem:
- Fine, blanching, red papules
- Starts on chest, axillae, groin within 12-48 hours
- Spreads to extremities within 24 hours
- Spares palms and soles
- Facial flushing with circumoral pallor
- Feels like sandpaper to touch
- Fades 3-4 days, followed by fine desquamation (especially hands/feet) lasting 2-3 weeks
Diagnosis
| Test |
Details |
| Rapid Antigen Detection Test (RADT) |
85-95% sensitive, 95% specific. Results in 5-10 minutes. |
| Throat Culture |
Gold standard. Required to confirm negative RADT in children 3-21 years. |
| Anti-streptococcal antibodies |
ASO, anti-DNase B. For retrospective diagnosis only. |
⚠️ Important: In children >3 years with negative RADT, obtain throat culture before withholding antibiotics (prevent acute rheumatic fever).
Complications
Suppurative Complications:
- Peritonsillar/retropharyngeal abscess
- Cervical lymphadenitis
- Otitis media, sinusitis
Nonsuppurative (Immune-Mediated):
- Acute Rheumatic Fever (ARF): 2-3 weeks post-infection. Jones criteria: carditis, polyarthritis, chorea, erythema marginatum, subcutaneous nodules
- Post-streptococcal Glomerulonephritis: 1-3 weeks post-infection. Hematuria, edema, hypertension
- PANDAS: Pediatric Autoimmune Neuropsychiatric Disorders
Management
Antibiotic Therapy (AAP/CDC Guidelines 2025)
First-Line Treatment:
Oral:
• Penicillin V: 250 mg PO BID-TID (≤27 kg) or 500 mg BID-TID (>27 kg) × 10 days
• Amoxicillin: 50 mg/kg/day (max 1000 mg) PO once daily × 10 days
IM (single dose):
• Benzathine penicillin G: 600,000 units (≤27 kg) or 1.2 million units (>27 kg)
Penicillin Allergy:
• Cephalexin: 20 mg/kg/dose PO BID (max 500 mg/dose) × 10 days
• Azithromycin: 12 mg/kg/day (max 500 mg) × 5 days
• Clindamycin: 7 mg/kg/dose PO TID (max 300 mg/dose) × 10 days
Supportive Care
- Antipyretics: Acetaminophen or ibuprofen
- Analgesics for throat pain
- Soft diet, cold liquids, throat lozenges
- Adequate hydration
Isolation
Droplet precautions. Exclude from school/childcare until afebrile AND 12 hours after starting antibiotics (24 hours in outbreak settings per AAP Red Book 2024-2027).
📚 Evidence Base: CDC Group A Strep Clinical Guidance August 2025, AAP Red Book 2024-2027.
Note: Penicillin remains drug of choice - NO resistance documented in Group A Strep.
Clinical Presentation
Incubation: 5-15 days (average 9-10 days)
Contagious: During febrile period; virus shed in saliva for weeks
Etiology: Human Herpesvirus 6B (>90%), HHV-7 (less common)
🔍 CLASSIC PATTERN (Pathognomonic):
High fever for 3-5 days → Rapid defervescence → Rash appears as fever resolves
"Exanthem subitum" = sudden rash
Febrile Phase (Days 1-5)
- Abrupt onset high fever (39.5-40.5°C / 103-105°F)
- Duration: 3-5 days
- NO localizing symptoms - key diagnostic clue
- Child often appears surprisingly well despite high fever
- Mild irritability, decreased appetite
- Periorbital edema may be present
⚡ Febrile Seizures in 10-15%:
• Due to high fever + HHV-6 neurotropism
• Usually simple febrile seizures
• No increased risk of epilepsy
• Manage fever aggressively
Rash (Post-Fever)
Appears as fever drops dramatically:
- Rose-pink, discrete macules/papules 2-3 mm
- Blanching, non-pruritic
- Begins on trunk/neck
- Spreads to face/proximal extremities
- Non-confluent
- Fades in 1-2 days without desquamation
- Present in only 20-30% of HHV-6 infections
Diagnosis
Clinical diagnosis based on classic presentation:
- Well-appearing infant 6-24 months
- High fever × 3-5 days with no localizing signs
- Fever resolves → rash appears
Laboratory testing rarely needed:
• PCR for HHV-6/HHV-7 DNA (if required)
• CBC: Leukopenia, neutropenia, relative lymphocytosis common
• Serology: IgM/IgG (rarely used)
Management
Supportive Care
Treatment is symptomatic:
• Antipyretics: Acetaminophen 15 mg/kg q4-6h OR Ibuprofen 10 mg/kg q6-8h
• Adequate hydration
• Reassurance: self-limited in immunocompetent hosts
• Monitor for dehydration and febrile seizures
• No antiviral therapy for immunocompetent children
Immunocompromised Patients
For severe disease (encephalitis):
- Ganciclovir or Foscarnet (off-label use)
- No controlled trials; case reports only
- Infectious disease consultation recommended
Isolation
No specific isolation required. Virus shed in saliva for weeks-months.
📚 Evidence Base: AAP guidelines, Merck Manual 2023-2025, StatPearls 2023.
Epidemiology: Accounts for 10-45% of febrile illness in infants <2 years. >95% seropositive by age 2-3 years.
Clinical Presentation
Incubation: 4-21 days (average 13-18 days)
Contagious: BEFORE rash appears (during viremia); NOT contagious once rash develops
Etiology: Parvovirus B19
🚨 2024 CDC ALERT: Major US outbreak
• IgM+ increased from <3% (2022-2024) to 10% (June 2024)
• Children 5-9 years: 15% → 40% in same period
• Increased complications in pregnant women and sickle cell patients
Prodrome (Often Absent/Mild)
- Low-grade fever (15-30%)
- Headache, malaise
- Myalgia, URI symptoms
- Appears 7-10 days before rash
🔍 PATHOGNOMONIC SIGN:
Slapped Cheek Appearance: Intense erythema of cheeks with circumoral pallor. Appears abruptly, most prominent in children.
Rash Evolution
Phase 1 (Days 0-1): Bright red facial erythema - "slapped cheeks"
Phase 2 (Days 1-4): Lacy, reticular, maculopapular rash on:
- Trunk and extremities
- May be pruritic
- Spares palms and soles
- Fades centrally creating characteristic lace-like pattern
Phase 3 (Weeks): Rash can recur with sun exposure, heat, exercise, stress for weeks
Diagnosis
Clinical: Distinctive slapped cheek + lacy body rash in child
| Test |
Details |
| Parvovirus B19 IgM |
Positive 3 days after symptoms, peaks 30 days, lasts 2-3 months. Confirms acute infection. |
| Parvovirus B19 IgG |
Indicates past infection/immunity. Appears 7 days after symptoms, persists lifelong. |
| PCR for B19 DNA |
Blood, amniotic fluid for immunocompromised or fetal infection |
| CBC |
Transient reticulocytopenia, anemia in susceptible patients |
Complications
⚠️ High-Risk Populations:
1. Polyarthropathy Syndrome:
- 60-80% adult women, 10% children
- Symmetric arthralgia/arthritis: hands, wrists, knees, ankles
- Duration: 1-3 weeks (can persist months)
2. Transient Aplastic Crisis:
- In chronic hemolytic anemias (sickle cell, thalassemia, spherocytosis)
- Severe anemia, reticulocytopenia
- Requires red blood cell transfusion
- CDC Alert: Increased cases in sickle cell patients 2024
3. Chronic Anemia:
- Persistent B19 infection in immunocompromised
- Pure red cell aplasia
- Treatment: IVIG
4. Hydrops Fetalis:
- Maternal infection weeks 13-20 gestation (highest risk)
- Fetal anemia → hydrops → fetal death in 2-6%
- Intrauterine transfusion may save fetus
Management
Immunocompetent Patients
Supportive care only - self-limited:
• Antipyretics: Acetaminophen or ibuprofen for fever
• NSAIDs for arthralgia in adults
• Antihistamines if rash pruritic
• Not contagious once rash appears - can return to school/work
Aplastic Crisis
- Red blood cell transfusion for severe anemia
- Usually recovers in 7-10 days
Immunocompromised (Chronic Anemia)
- IVIG: 400 mg/kg/day × 5-10 days for persistent infection
Pregnancy Management
🤰 Pregnant Woman Exposed:
1. Check B19 IgM/IgG immediately and 4 weeks later
2. If acute infection confirmed: Serial fetal ultrasounds for 8-12 weeks to detect hydrops
3. Hydrops detected: Consider intrauterine transfusion (fetal medicine consultation)
4. Most infected fetuses have good outcomes
Prevention
- No vaccine available (in development)
- Standard precautions, hand hygiene
- 50% household, 20-50% school/childcare transmission
- Pregnant healthcare/childcare workers: Use standard precautions, no need to exclude from work
- High-risk patients (chronic hemolytic anemia): Avoid exposure during outbreaks
📚 Evidence Base: CDC HAN Alert August 2024, AAP Red Book 2024, WHO.
2024 Outbreak: Significant increase across US and 14 European countries. Monitor high-risk populations closely.
Clinical Presentation
Incubation: 10-21 days (average 14-16 days)
Contagious: 1-2 days before rash until ALL lesions crusted (4-7 days)
Etiology: Varicella-Zoster Virus (VZV)
Prodrome
Mild in children (more prominent in adults/adolescents):
- Low-grade fever (38-39°C)
- Malaise, anorexia
- Headache
- Appears 1-2 days before rash
🔍 PATHOGNOMONIC FEATURE:
"Dew drop on a rose petal": Delicate vesicle on erythematous base
Hallmark: Lesions in DIFFERENT STAGES simultaneously (macules, papules, vesicles, pustules, crusts)
Rash Evolution
Distribution: Scalp/face/trunk (centripetal) → extremities (sparse on distal limbs, usually spares palms/soles)
Progression:
- Macule (few hours) → Papule (3-4 mm) → Vesicle (12-24 hours, "dewdrop") → Pustule → Crust (24-48 hours)
- New lesions appear in crops for 3-5 days
- Intensely pruritic
- Unvaccinated: 250-500 lesions
- Breakthrough varicella (post-vaccine): <50 lesions, often maculopapular without vesicles
Diagnosis
Clinical diagnosis usually sufficient in immunocompetent children with characteristic vesicular rash in different stages.
| Test |
Indication |
| PCR for VZV DNA |
Preferred. Vesicle fluid, scab, respiratory secretions. Most sensitive. |
| Direct Fluorescent Antibody (DFA) |
Vesicle scraping. Rapid but less sensitive than PCR. |
| Serology (IgM, IgG) |
4-fold IgG rise acute/convalescent. Not reliable in immunocompromised. |
Complications
⚠️ Complications:
Bacterial Superinfection (Most Common):
- Group A Strep, S. aureus (including MRSA)
- Cellulitis, abscess, necrotizing fasciitis
Pneumonia:
- 1 in 400 adults, rare in children
- Presents day 3-5
- Risk: Smoking, pregnancy, immunocompromised
Encephalitis (1-2:10,000):
- Cerebellar ataxia (children, benign)
- Acute encephalitis (adults, 5-10% mortality)
Other:
- Reye syndrome: AVOID ASPIRIN in children
- Hemorrhagic varicella: Immunocompromised, high mortality
- Congenital varicella syndrome: Maternal infection 8-20 weeks gestation
- Neonatal varicella: Maternal infection -5 to +2 days of delivery (30% mortality if untreated)
Management
Healthy Children
Symptomatic care - self-limited:
• Antipruritics: Calamine lotion, cool baths with colloidal oatmeal, oral diphenhydramine or hydroxyzine
• Antipyretics: Acetaminophen ONLY (AVOID ASPIRIN - Reye syndrome; AVOID ibuprofen - possible increased bacterial infection risk)
• Prevent scratching: Trim nails, mittens for infants
• Keep lesions clean and dry
• Antiviral NOT routinely recommended in healthy children
High-Risk Patients Requiring Antiviral Therapy
Indications for Acyclovir:
• Age >12 years
• Chronic cutaneous/pulmonary disorder
• Chronic salicylate therapy
• Corticosteroid therapy
• Immunocompromised
• Pregnant women
• Neonatal varicella
Dosing:
• Oral: Acyclovir 20 mg/kg/dose (max 800 mg) PO QID × 5 days. Start within 24 hours of rash onset.
• IV: Acyclovir 10 mg/kg q8h (500 mg/m² q8h) × 7-10 days for severe disease, immunocompromised, pneumonia
Isolation
Airborne + Contact precautions. Exclude from school/childcare until ALL lesions crusted. Healthcare: Negative pressure room.
Post-Exposure Prophylaxis
- Vaccine within 3-5 days: 70-90% protective. For ≥12 months without immunity
- VariZIG within 10 days: Immunocompromised, pregnant women, neonates. 125 units/10 kg IM (max 625 units)
Prevention
💉 Varicella Vaccine (Live Attenuated):
• Dose 1: 12-15 months
• Dose 2: 4-6 years
• Efficacy: 90% against all varicella, 98% against severe disease
Contraindications: Severe immunodeficiency, pregnancy, recent IVIG/blood products
Breakthrough Varicella: Mild (<50 lesions). Contagious until no new lesions × 24 hours.
📚 Evidence Base: CDC Clinical Guidance July 2024, AAP Red Book 2024-2027.
Impact: Pre-vaccine: 3.5 million cases/year in US. Post-vaccine: <10,000/year. Vaccine prevented 91 million cases, 238,000 hospitalizations, 2,000 deaths (1995-2019).
Clinical Presentation
Incubation: 3-6 days
Contagious: Most contagious first week; virus shed in stool 2-8 weeks
Etiology: Enteroviruses (Coxsackie A16, CVA6, Enterovirus A71)
Prodrome
- Low-grade fever (38-39°C)
- Malaise, irritability
- Decreased appetite
- Sore throat
- Appears 1-2 days before rash
🔍 PATHOGNOMONIC TRIAD:
1. Fever
2. Oral lesions (painful vesicles → ulcers)
3. Peripheral rash (hands, feet, sometimes buttocks)
Oral Lesions
- Painful vesicles on tongue, buccal mucosa, palate
- Progress to shallow ulcers 2-8 mm
- Cause refusal to eat/drink
- Most prominent symptom in young children
Cutaneous Rash
Classic HFMD:
- Papulovesicular rash on palms (including thenar/hypothenar), soles, dorsal hands/feet
- Sometimes buttocks, perioral area
- Vesicles 2-10 mm on erythematous base
- Elliptical shape (characteristic)
- Non-pruritic usually
- Resolves 7-10 days
⚠️ Atypical HFMD (Coxsackie A6):
• Widespread vesiculobullous rash
• Eczema coxsackium: Superinfection of atopic dermatitis areas
• More severe/extensive lesions
• High fever
• Onychomadesis: Nail shedding 3-8 weeks later (benign, regrows)
Diagnosis
Clinical diagnosis based on characteristic distribution: oral ulcers + hand-foot rash in young child with fever
| Test |
When Used |
| RT-PCR for enterovirus RNA |
Throat swab, rectal swab, vesicle fluid, stool. Most sensitive. For atypical/severe cases. |
| Enterovirus typing/sequencing |
Public health labs. Identifies specific serotype (CVA16, CVA6, EV-A71) |
Complications
Usually mild and self-limited. Complications more common with EV-A71:
Common Complications:
- Dehydration: Most common - due to refusal to eat/drink from painful oral ulcers
- Onychomadesis: Nail shedding 3-8 weeks post-infection (especially CVA6). Benign, nails regrow
- Aseptic meningitis: More common with EV-A71. Usually benign, resolves without sequelae
Severe Neurologic Complications (EV-A71):
- Brainstem encephalitis
- Acute flaccid paralysis
- Neurogenic pulmonary edema
- Can be fatal
- Presents: Myoclonus, tremor, ataxia, cranial nerve palsies, cardiopulmonary failure
Warning Signs (Require Hospitalization):
- Persistent high fever
- Myoclonus, tremor, ataxia
- Rapid breathing/tachycardia
- Altered consciousness
Management
Supportive Care
Treatment is symptomatic - self-limited in 7-10 days:
Pain Management:
• Acetaminophen or ibuprofen (AVOID aspirin in children)
• Topical: "Magic mouthwash" (diphenhydramine + antacid), viscous lidocaine >6 years (use cautiously)
• Honey for throat pain >1 year
Hydration:
• Encourage cold, bland fluids (avoid acidic/spicy)
• Popsicles, ice chips, soft foods
• Monitor for dehydration - may require IV fluids if severe
Oral Care:
• Soft diet
• Avoid hot/spicy/salty/acidic foods
Severe Disease (EV-A71)
No specific antiviral therapy proven effective. In severe cases (Asia):
- IVIG (limited evidence)
- Milrinone for neurogenic pulmonary edema (limited evidence)
- Intensive care support
Isolation
Droplet + Contact precautions if hospitalized. Exclude from daycare/school until fever-free and oral lesions healing.
Prevention
Hygiene Measures (Most Important):
- Handwashing with soap and water (alcohol sanitizers LESS effective against non-enveloped enteroviruses)
- Disinfect surfaces/toys with EPA-registered disinfectant for non-enveloped viruses (bleach solution)
- Avoid close contact (kissing, hugging, sharing utensils/cups)
- Good diapering hygiene
- Respiratory etiquette
Vaccination
- EV-A71 vaccines licensed in China (2015)
- NOT available in US
- Does not provide cross-protection against other enterovirus serotypes
Outbreak Control
In severe outbreaks (especially Asia): Isolation of cases, social distancing, school/daycare closures
📚 Evidence Base: CDC Yellow Book 2024, WHO PAHO Epidemiological Alert March 2025.
Geographic Distribution: Worldwide. Asia-Pacific: EV-A71 predominant (more severe). US/Europe: CVA16, CVA6 predominant. 2025 Outbreaks: Reported in US Virgin Islands, Peru, Guyana, Trinidad & Tobago.