Roseola Infantum
Summary
Roseola infantum, also known as Exanthem Subitum or Sixth Disease, is a common benign viral exanthem of early childhood caused primarily by Human Herpesvirus 6 (HHV-6) and less commonly HHV-7. It is characterized by a specific clinical course: a sudden high fever (often >39°C) persisting for 3-5 days which abruptly resolves, followed immediately by the appearance of a maculopapular rash. It is a major cause of febrile seizures in infants under 2 years of age.
Key Facts
- Definition: Acute viral infection of infants characterized by high fever followed by a rash upon defervescence.
- Prevalence: Near universal infection (>90%) by age 2-3 years.
- Mortality/Morbidity: Generally benign; primary morbidity arises from febrile seizures (occur in 10-15% of cases).
- Key Management: Supportive care (hydration, antipyretics) and reassurance.
- Critical Threshold: Seizure duration >5 minutes requires acute management.
- Key investigation: Clinical diagnosis; investigations rarely indicated unless ruling out sepsis.
Clinical Pearls
The "Well" Febrile Infant: A classic feature is an infant with a very high fever (39-40°C) who appears surprisingly well, alert, and playful when the fever is actively controlled.
The "Defervescence Rash": The rash of Roseola is unique because it appears after the fever stops. If the rash appears while the fever is still high, consider Measles or Kawasaki disease.
Nagayama Spots: Look for erythematous papules on the soft palate and uvula (Nagayama spots); present in ~65% of cases and can help differentiate from other viral exanthems.
Why This Matters Clinically
Roseola is one of the most common causes of acute febrile illness and emergency department visits in infants 6-18 months old. Recognizing the classic pattern avoids unnecessary antibiotic use, lumbar punctures, and hospital admissions for suspected sepsis. It is also the most common identifiable trigger for a first febrile seizure.
Incidence & Prevalence
- Incidence: Extremely common; virtually all children are infected by age 3.
- Prevalence: Seroprevalence of HHV-6 is >90% in adults.
- Trend: Stable endemic infection; no clear seasonal variation (unlike Influenza or RSV).
Demographics
| Factor | Details |
|---|---|
| Age | Peak incidence 6 to 15 months. Rare <3 months (maternal antibodies) or > years. |
| Sex | Male:Female ratio is approximately 1:1. |
| Ethnicity | Occurs worldwide in all ethnic groups. |
| Geography | Global distribution. |
Risk Factors
Non-Modifiable:
- Age: Being between 6 months and 2 years.
- Immune status: Immunocompromised children may have severe or atypical disease.
Modifiable:
- Childcare attendance: Increased exposure risk (though transmission is often from asymptomatic adult saliva).
- Siblings: Close contact with older siblings.
| Risk Factor | Relative Risk |
|---|---|
| Age 6-15 months | High (Primary window of vulnerability) |
| Daycare attendance | Moderate increase in exposure |
Mechanism
Step 1: Viral Entry & Replication
- Agent: Human Herpesvirus 6 (variants A and B, with B causing 99% of Roseola) or HHV-7.
- Transmission: Respiratory droplets or saliva (often from asymptomatic caregivers causing horizontal transmission).
- Entry: Virus enters via oropharynx, replicates in salivary glands.
Step 2: Viraemia & Dissemination
- Incubation: 9-10 days (range 5-15 days).
- Viraemia: Virus infects T-lymphocytes (CD4+ T cells) causing high-grade viraemia.
- Cytokine Storm: Induction of cytokines (IFN-alpha, TNF-alpha, IL-1beta) correlates with the rapid onset of high fever.
Step 3: Clinical Manifestation (Rash)
- Defervescence: Fever falls as host immunity (antibodies + cellular response) clears viraemia.
- Rash Mechanism: The rash is believed to be an immune complex-mediated reaction (antigen-antibody deposition in skin) rather than direct viral replication in skin cells.
- Latency: Like all herpesviruses, HHV-6 establishes lifelong latency in T-cells and monocytes.
Classification
| Stage | Definition | Clinical Features |
|---|---|---|
| Incubation | Post-exposure replication | Asymptomatic (approx. 10 days). |
| Febrile Phase | Active viraemia | Sudden onset high fever (39-40.5°C), irritability, lymphadenopathy. |
| Exanthem Phase | Immune clearance | Fever resolves abruptly; maculopapular rash appears centrally. |
Anatomical/Physiological Considerations
The Developing Brain: The immature infant brain is more susceptible to fever-induced lowering of the seizure threshold. HHV-6 is also neurotropic and has been detected in CSF during febrile seizures, suggesting direct CNS invasion may play a role beyond simple febrile threshold.
Symptoms
Typical Presentation:
Atypical Presentations:
Signs
Red Flags
[!CAUTION] Red Flags — Seek immediate help if:
- Non-blanching rash: Indicates petechiae/purpura (Meningococcal sepsis).
- Prolonged seizure: >5 minutes (Status Epilepticus).
- Decreased consciousness: Lethargy, difficult to wake.
- Bulging fontanelle: Sign of raised ICP (Meningitis).
- Fever >5 days: Consider Kawasaki disease or other bacteria.
Structured Approach
General:
- ABCDE Assessment: Prioritize Airway/Breathing/Circulation if child is seizing or drowsy.
- Hydration Status: Check capillary refill, mucous membranes, skin turgor.
- Alertness: "Tickle test" or toy interaction to assess neurological status.
Specific System Examination:
- Skin: Perform "glass test" (diascopy) to ensure rash blanches. Check distribution (Trunk > Face).
- ENT: Inspect throat for Nagayama spots. Check ears to rule out bacterial otitis media.
- Neurology: Check for neck stiffness (meningism) and fontanelle tension.
Special Tests
| Test | Technique | Positive Finding | Sensitivity/Specificity |
|---|---|---|---|
| Glass Test | Press clear glass against rash | Rash disappears (blanches) | High specificity for ruling out purpura |
| Fontanelle Check | Palpate anterior fontanelle (sitting up) | Soft and flat (Normal) vs Bulging (Meningitis) | Crucial in infants |
| Kernig's Sign | Flex hip 90°, extend knee | Pain/resistance (Meningitis) | Low sensitivity in infants |
First-Line (Bedside)
- Urinalysis: Essential in all febrile infants without a clear focus to rule out UTI.
- Blood Glucose: Check if drowsy or seizing (rule out hypoglycaemia).
Laboratory Tests
Routine bloods are generally NOT required for classic Roseola.
| Test | Expected Finding | Purpose |
|---|---|---|
| FBC | Leukopenia (low WBC) with lymphocytosis | Viral pattern; helps exclude bacterial sepsis. |
| CRP | Normal or mild elevation | Exclude severe bacterial infection. |
| Blood Culture | Negative | Only indicated if sepsis suspected. |
| Urine Culture | Negative | Rule out UTI. |
Imaging
Imaging is rarely indicated.
| Modality | Findings | Indication |
|---|---|---|
| CXR | Normal | Only if significant respiratory distress/signs. |
| CT/MRI Brain | Normal (unless complications) | Only for complex seizures or focal neuro signs. |
Diagnostic Criteria
Diagnosis is primarily clinical based on the classic sequence:
- High fever (3-5 days) in a well-appearing infant.
- Defervescence (fever stops).
- Appearance of characteristic rose-pink rash on trunk.
Management Algorithm
Acute/Emergency Management (Seizures)
Immediate Actions (Febrile Convulsion):
- Safety: Place child in recovery position; remove dangerous objects.
- Timing: Note start time. Most stop within 2-3 mins.
- Airway: Ensure airway is patent. Do not put anything in mouth.
- Medication: If >5 mins, Administer:
- Buccal Midazolam: 0.5mg/kg
- Or Rectal Diazepam: 0.5mg/kg
- Call for Help: Ambulance if first seizure or >5 mins.
Conservative Management
- Reassurance: Explain the benign nature ("It will get better on its own").
- Hydration: Encourage frequent breastfeeds or clear fluids.
- Environment: Keep child cool and comfortable; avoid over-bundling.
- Exclusion: Keep away from childcare until systemic symptoms resolve (rash itself is not contagious—viraemia has passed).
Medical Management
Antibiotics are NOT indicated.
| Drug Class | Drug | Dose | Duration |
|---|---|---|---|
| Antipyretic | Paracetamol | 15mg/kg Q6H (Max 60mg/kg/day) | PRN for distress |
| NSAID | Ibuprofen | 10mg/kg Q8H (Max 30mg/kg/day) | PRN for distress (> months old) |
Surgical Management
Not applicable.
Disposition
- Admit if: First febrile seizure (observation), bacterial sepsis cannot be excluded, severe dehydration.
- Discharge if: Classic presentation, well hydrated, re-assuring parents.
- Follow-up: GP review if fever persists >5 days or rash becomes non-blanching.
Immediate (Minutes-Hours)
| Complication | Incidence | Presentation | Management |
|---|---|---|---|
| Febrile Seizure | 10-15% | Tonic-clonic activity, loss of consciousness | airway protection, benzos if prolonged |
| Dehydration | Common | Dry mucous membranes, reduced wet nappies | Oral rehydration solution |
Early (Days)
- Aseptic Meningitis: Rare. Headache, lethargy, photophobia. Usually self-limiting.
- Encephalitis: Very rare. Altered mental status. Requires antivirals (Ganciclovir/Foscarnet) in immunocompromised.
Late (Weeks-Months)
- Mesial Temporal Sclerosis: Controversial potential link between prolonged HHV-6 febrile seizures and later temporal lobe epilepsy (research ongoing).
Natural History
Roseola is a self-limiting illness.
- Fever Phase: 3-5 days.
- Rash Phase: 1-2 days (sometimes only hours).
- Full Recovery: usually within a week.
Outcomes with Treatment
| Variable | Outcome |
|---|---|
| Mortality | Extremely rare in healthy children. |
| Morbidity | Low (seizures are terrifying for parents but benign). |
| Recurrence | Second episodes possible (HHV-7 infection) but rare. |
| 5-year survival | ~100% |
Prognostic Factors
Good Prognosis:
- Immunocompetent host.
- Typical "well" appearance between fever spikes.
- Rapid resolution of rash.
Poor Prognosis:
- Immunocompromised state (risk of bone marrow suppression, pneumonitis, encephalitis).
- Prolonged status epilepticus.
Key Guidelines
- NICE CKS (2024) — Viral rash in pregnancy and childhood. Recommends supportive care and exclusion of serious causes. NICE
- American Academy of Pediatrics (2011) — Neurodiagnostic evaluation of the child with a simple febrile seizure. Evidence against routine lumbar puncture in vaccinated children. AAP
Landmark Trials
Hall et al. (1994) — HHV-6 is main cause of emergency visits.
- 2000+ patients.
- Key finding: HHV-6 accounted for 20% of ED visits for fever in infants 6-12 months.
- Clinical Impact: Established Roseola as a major public health entity, not just a rash.
Yamanishi et al. (1988) — Identification of HHV-6 as cause of Exanthem Subitum.
- Key finding: Isolated the virus from lymphocytes of patients.
- Clinical Impact: Confirmed etiology.
Evidence Strength
| Intervention | Level | Key Evidence |
|---|---|---|
| Antipyretics for comfort | 1a | Cochrane Reviews (Paracetamol/Ibuprofen efficacy) |
| Antibiotics | 1a (Against) | Multiple studies proving viral etiology |
| Routine LP for simple seizure | 2a (Against) | AAP Guidelines |
What is Roseola?
Roseola (often called "Sixth Disease") is a very common viral infection in babies and toddlers. It is famous for causing a sudden high fever that lasts a few days, followed by a pink rash just as the fever breaks. It is almost a "rite of passage" for childhood.
Why does it matter?
While usually harmless, the high fever can be frightening for parents and can sometimes trigger a "febrile convulsion" (a seizure caused by high temperature). The good news is that once the rash appears, the child is usually getting better and is no longer contagious.
How is it treated?
- Comfort: Use Paracetamol or Ibuprofen if the child is miserable or in pain. Treating the fever number itself is not necessary if the child is happy.
- Hydration: Offer plenty of breastmilk, formula, or water.
- Patience: Antibiotics do not work because it is a virus. It will go away on its own.
What to expect
- Days 1-3: High fever, maybe fussy, but plays in between.
- Day 4: Fever disappears suddenly.
- Day 5: Pink, spotty, non-itchy rash appears on tummy/back.
- Day 6-7: Rash fades, child back to normal.
When to seek help
- If the child has a seizure (convulsion).
- If the rash does not fade when pressed under a glass (glass test).
- If the baby is floppy, unresponsive, or not drinking fluids.
- If the fever lasts more than 5 days.
Primary Guidelines
- Stone RC et al. Viral exanthems. Dermatol Online J. 2015;21(12):13030/qt98b6775z. PMID: 26990473
Key Trials
- Hall CB et al. Human herpesvirus 6 infection in children. A prospective study of complications and reactivation. N Engl J Med. 1994;331(7):432-8. PMID: 8035839
- Yamanishi K et al. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet. 1988;1(8594):1065-7. PMID: 2896909
- Tesini BL et al. Human Herpesviruses 6 and 7. Principles and Practice of Pediatric Infectious Diseases. 2018.
Further Resources
- DermNet NZ: Roseola Infantum
- Radiopaedia: Human herpesvirus 6
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.