FEVER and RASH

Yinghu Chen

Dept. Infection Disease

Email: Chenyinghu@sina.com

Pediatrics

Rash and infections

Rashes are a common manifestation of many infections.

Skin lesions provide important clues to the diagnosis Macular or Maculopapular Rash

Diffuse Erythroderma

Urticarial Rash

Vesicular, Bullous, Pustular

Petechial-Purpuric

Erythema Nodosum

Differential Diagnosis of Fever and Rash

Macular or Maculopapular Rash -- virus

Measles

Rubella

Roseola (HHV-6 or HHV-7)

Varicella-Zoster virus (VZV)

Differential Diagnosis of Fever and Rash

Macular or Maculopapular Rash--bacteria

Scarlet fever (group A streptococcus)

Others: Secondary syphilis, Leptospirosis, 

Pseudomonas, Meningococcal infection (early),

Salmonella typhi (typhoid fever), Lyme disease

(erythema migrans), Mycoplasma pneumoniae

Measles

Outline

EtiologyEpidemiologyPathogenesisClinical manifestationsLab findingsTreatmentComplicationsPreventions

Introduction

Historically widespread but now very rareCharacterized by fever, coryza, cough, Koplik’s

spots, and maculopapular rash

Etiology

Measles virus, a single-stranded RNA paramyxovirus with one serum type. Humans are the only natural host

Found in nasopharyngeal secretions, blood and urine, during the prodromal period and for a short time after the rash appears

Remain active for 1-2 days at room temperature

Epidemiology

Spread throughout the world, vaccine-preventable disease For susceptible persons, 90% of the exposed acquire disease Infection sources: patients and person with latent infection Contagious period: 5 days before and after the rash appearance,

accompanied with pneumonia, prolonging to 10th day Transmission: airborne and contact Season: spring, Age: 5-10yr New trends: measles appears in <8m infants and elders, due to

inadequate vaccination as well as vaccine failure

Pathogenesis

Process of virus in the body (two times of viremia)

Invade airway endothelial cells, portal lymph node, and multiply (warthin-Finkeldey giant cell)

Some invade to blood Captured by Monocyte - macrophage

system, and replicates greatly, Invade blood second time, cause

disseminated lesions, some target T cells

The host immunity decrease, induce secondary bacterial infection and TB reactivation

Endothelial cells

Dendritic cell

T cells

Pathogenesis

Process of virus in the body Clinical stage

Virus inhalation

IncubationLocal proliferation

First viremia

Proliferation in endoreticular system

Second viremia Prodromal

All parts of the body Eruption

Clearance of virus Convalescence

Clinical manifestaions

Persons with typical symptoms immunocompetent children who didn’t receive measles

vaccine, or vaccine failure, and didn’t receive immunoglobulin

Four stages Incubation stage: 6-12d, may transmit virus by 9-10th day Prodromal stage: 3-5d, fever, cough, coryza, Koplik spots Rash stage: rash erupts for 2-3d , and fades Recovery stage

Prodromal stage

Last 3-5d, low-grade to moderate fever, dry cough, coryza, and conjunctivitis, photophobia, Koplik spots.

Koplik spots and Stimson line

Koplik spots: 1-2d before rash, grayish white dots, as small as grains, opposite the lower molars, may spread over the buccal mucosa, last 12-24hr

Rash stage

Temperature rises abruptly as the rash appears and often reaches 40 or higher℃

The rash appears and fade downward sequence: stars (faint macules) on the upper lateral part of neck, behind the ears, along the hairline, cheek, spreads to entire face (maculopapular), neck, upper arms, chest back, abdomen, entire arm, thighs, and finally reach feet on the 2nd-3rd day

In uncomplicated cases, as the rash appears on the legs and feet, the patients may appear desperately ill, but the symptoms subside within 2d

Branny desquamation within 7-10d

Black measles

Hemorrhagic type of measles Bleeding may occur from mouth, nose, or

bowel, thrombocytopenia Occurs in immunocompromised or

secondly infection patients

Rash is confluent, petechiaeOften accompanied with

pneumonia, heart failure, disseminated intravascular coagulation (DIC), high mortality

Mild measles

Mild casesOccurs in person with partial protection

against measles, such as vaccine, immuoglobulin

Atypical measles

Partial protection against measles, such as vaccine.

Fever 2-3 days, appearance of the rash.

The eruption order: the distal limbs, trunk and face.

Mild case.

Laboratory findings

Cytopathic change Warthin-Finkeldey cells: consist of multinucleated giant

cells with intranuclear inclusionsAntigen: in nasal mucosaPCR Virus isolationAntibodies

IgM and IgG become detectable when the rash appears

Leucocytopenia with a relative lymphocytosis

Chest radiograph

May show interstitial or perihilar infiltrates, but do not distinguish measles pneumonia and bacterial superinfection.

Diagnosis

Contact historyCharacteristic clinical pictureLaboratory confirmation is rarely needed

Differential diagnosis

All kind of fever with red rashesSuch as: Rubella, roseola, scarlet fever,

meningococcemia, drug fever, Kawasaki disease, serum sickness, infectious mononucleosis, toxoplasmosis, etc

Differential diagnosis

Enteroviral and adenoviral infections, rubella: The rashes are less striking without desquamation

Roseola infantum: the rash appears as fever disappears

Serum illness and drug fever: The absence of administration of a drug history

Red rash in bacterium infection

Acute meningococcemia The rash is petechial, and purpuric without cough and conjunctivitis

Streptococcal scarlet fever The diffuse, finely papular rash has a “goose flesh” texture, “sandpaper”

texture, strawberry tongue, red pharynx. Perioral and periorbital area, palm, and soles have no rash. Rash desquamates after 7-14d

Staphylococcal scarlet fever Resembles streptococcal scarlet fever Except strawberry tongue, pharynx, and focal infection usually presents

Treatment

No specific antiviral therapy Supportive treatment: antipyratic, bed rest, fluid intake,

avoiding exposure to strong lights Vitamin A: 7-12m infant: 100,000IU, ≥1y: 200,000IU,

reduce the morbidity and mortality Complications such as encephalitis, giant cell

pneumonia, DIC must be assessed individually Secondary infection requires antimicrobial therapy Immune globulin and corticosteroids has limited value

Vitamin A and measles: evidence

Hyporetinemia is present in over 90% of measles

cases in Africa and 22-70% in USA.

There is an apparent inverse correlation between

retinol concentration and the severity of measles.

Oral Vitamin A supplement reduces the morbidity and

mortality of severe cases.

Indication for Vit A supplement

(American Academy of Pediatrics)

Hospitalized children 6mo~2yr of ages

Children >6mo with immunodeficiency

ophthalmologic evidence of Vit A deficiency

impaired intestinal absorption

moderate to severe malnutrition

recent immigration from areas with a high mortality from measles

Complication

Pneumonia Interstitial pneumonia: may be caused by measles virus

(giant cell pneumonia), measles pneumonia in HIV-infected patients is often fatal.

However, bacterial superinfection and bronchopneumonia is more frequent

Reactivation of TB infection, and anergy to PPD Myocarditis

An infrequent serious complication, varies from transient electrocardiographic changes to heart failure, and cardiogenic shock

Complication in nervous system

Eary encephalitis 1-2/1000 cases, occur from prodromal period to final stage

Late encephalitis Demyelinization, probably an immunopathologic phenomenon.

Subacute sclerosing panencephalitis (SSPE) A chronic encephalitis caused by persistant measles virus

infection of the central nervous system, occur 8-10yr after measles

Insidiously onset, subtle changes in behavior, and deterioration of schoolwork, and finally dementia.

1/1,000,000 measle

Prognosis

Deaths: bronchopneumonia or encephalitis(15%), with malignancy or HIV infection

SSPE

Prevent

Attenuate live measle vaccine Two times(8m, 4-6yr), not booster, but intensive

immunization

Contraindications: Immunocompromised states, pregnancy or recent

administration of IVIg

Postexposure prophylaxis

Vaccine within 72 hr (produce antibody within 7-12d)

Immune globulin within 6d

Typical temperature curve of measles and the effectiveness of passive immunization

Take home points

Koplik spotsFeature of measles maculopapular rashDifferential diagnosis of red rashComplicationsPost exposure prophylaxis

Rubella

Rubella

also known as German measles and 3-day

measles;

congenital rubella syndrome (infection in

utero )

Etiology and epidemiology

a single-stranded, positive-sense RNA virus, togavirus

family, one serum type.

Humans as the only host

Spread either by oral droplet or transplacentally to

fetus causing congenital infection

Contagious period: 5 days before until 7 days after

onset of the rash.

Peak incidence in children 1~5 yr of age

Clinical manifestations

Incubation stage (14 to 21 d)

Prodromal stage (1-2d)

Mild catarrhal symptoms with shorter period

Low-grade fever (1~3d) with mild systemic symptoms.

About 2/3 are subclinical.

Eruption stage

Eruption stage

The most characteristic sign ：

Enlarged post-occipital, retroauricular and

posterior cervical lymph nodes accompanied by a

maculopapular, discrete rash.

The rash begins after 1-2d of fever, on the face and

spreads to the body in 1d and lasts for 3 days.

Congenital rubella (syndrome)

Affects virtually all organ systems

The common manifestation is: intrauterine growth retardation

Never system: microcephaly, deafness

Eye: microphthalmia, cataracts, glaucoma, chorioretinitis

Blood system: anemia, thrombocytopenia, leukopenia,

Skin and others: blueberry muffin rash, hepatosplenomegaly, jaundice, PDA

B cell and T cell deficiency infant may be asymptomatic at birth.

Diagnosis

Apparent diagnosis based on clinical symptoms and

signs

Laboratory findings non-specific and generally do not aid

in diagnosis

Confirmed by serology or virus culture

Congenital rubella: serum IgM or virus culture

Prenatal diagnosis: cord blood IgM or virus culture

from amniotic fluid

Treatment and prognosis

There is no specific antiviral therapy

Entirely supportive, and antipyretics

The prognosis is excellent, but congenital rubella

syndrome may have sequalae such as intrauterine

growth retardation, cataracts, deafness, and PDA.

Prevention

Live rubella vaccine recommended as MMR for

children( initial at 12-15m and second 4-6y)

It is important for girls to have immunity before they

reach childbearing age.

Roseola infantum

Etiology

Human herpesvirus (HHV) type 6 (HHV-6), HHV-7.

Large, enveloped double-stranded DNA viruses, members of

the herpesvirus family.

Infect mature mononuclear cells and cause a relatively

prolonged (3 to 5 days) viremia during primary infection.

Be detected in the saliva of healthy adults, which suggests, the

development of lifelong latent infection and intermittent

shedding of virus.

Epidemiology

Transplacental antibody protects most infants until 6 months of age.

Primary HHV-6 infection occurs early in life with peak acquisition from

6-15 months of age.

By 12 months of age, approximately 60% to 90% of children have

antibodies to HHV-6, and essentially all children are seropositive by 2 to

3 years of age.

The virus is likely acquired from asymptomatic adults who periodically

shed these viruses..

HHV-6 and HHV-7 can cause encephalitis in immunocompromised

persons.

HHV-6 can be transmitted in utero.

Cinical manifestations

Incubation period: 5-10d

Prodromal period:

Usually asymptomatic

Mild URT signs

Mild cervical lymphadenopathy

Cinical manifestations

Clinical illness heralded by high fever

37.9~40.0 with an average of 39℃

Persists for 3-5 days and then resolves rather abruptly.

Occasionally fever diminish over 24-36h gradually.

May be irritable and anorexia but most behave normally

Seizures in 5~10%. Roseola is associated with approximately one t

hird of febrile seizures.

Infrequent : rhinorrhea, sore throat, abdominal pain, vomiting and

diarrhea.

Cinical manifestations

Eruption and fever

A rash appears within 12~24 hours of fever

resolution

Eruption during defervescence or within a few

hours of fever resolution

Cinical manifestations

Characteristic rash

Rose colored rash ( discrete, small (2~5mm),slightly raised pink lesions)

appears trunk , neck, behind ears, face and proximal extremities

No pruritic, no vesicles

Fade in 1~3 days

Reactivation of HHV-6 may cause bone marrow suppression after bone marrow

transplantation

Treatment and prevention

There is no specific therapy

HHV-6 is inhibited by ganciclovir but the

benign nature preclude consideration of

antiviral therapy.

Excellent prognosis in majority

no guidelines for prevention of roseola.

Varicella

Etiology

Varicella-zoster virus (VZV): an enveloped, double-stranded

DNA virus that is a member of the herpesvirus family.

Humans are the only natural host.

Chickenpox (varicella) is the manifestation of primary infection

of varicella-zoster virus (VZV).

Zoster (shingles) is the manifestation of reactivated latent

infection of endogenous VZV.

Epidemiology

Spread throughout the world, vaccine-preventable disease For susceptible persons, 90% of the exposed acquire disease Infection sources: patients and person with latent infection Contagious period: 2 days before to 7 days after the onset of the rash Transmission: droplet, air, direct contact.

Incidence of Zost: Approximately 10% to 20% of chickenpox Only 5% of cases of zoster occur in children <15 years old 75% of cases occurring after 45 years of age. The incidence of zoster is increased among immunocompromised persons.

Pathogenesis

Process of virus in the body (two times of viremia) VZV infects individuals via the conjunctivae or respiratory tract

and replicates in the nasopharynx and upper respiratory tract. It disseminates by a primary viremia and infects regional lymph

nodes, the liver, the spleen, and other organs. A secondary viremia follows, resulting in a cutaneous infection

with the typical vesicular rash.

After resolution of chickenpox, the virus persists in latent infection in the dorsal root ganglia cells.

Clinical manifestation

Incubation period: 10~21d

Subclinical varicella is rare

Prodromal symptoms

Usually moderate fever

malaise, headache, anorexia and occasionally

mild abdominal pain

precede the rash by 24~48h

Clinical manifestation

The characteristic rash

initially as small red papules

rapidly progress to nonumbilicated, oval, "teardrop" vesicles on an erythematous base.

The fluid progresses from clear to cloudy, and the vesicles ulcerate, crust, and heal.

New crops appear for 3 to 4 days, usually beginning on the trunk followed by the head, the face, and, less commonly, the extremities.

Clinical manifestation

Pruritus, mucous membrane lesions,

lymphadenopathy

Hypopigmentation or hyperpigmentation persists

for days to weeks in some

Scarring unusual unless secondarily infected

Clinical manifestation

Progressive varicella

usually in immunocompromised children, complicated with pneumonia, hemorrhagic, DIC.

Neonatal chickenpox

Delivery within 1 week before or after the onset of maternal varicella frequently results in severe hemorrhagic varicella in neonates at 5~10 days old, accompanied by fever, often involving the lung and liver, the mortality rate is as high as 30%.

Congenital varicella

when pregnant women (especially between 8-20 weeks) contract chickenpox, 2% of the fetuses may become infected. accompanied with cicatrix, limb hypoplasia, eye abnormalities, central nervous system damage, low birth weight.

Complication

Complications are common Secondary infection of skin lesions. Thrombocytopenia and hemorrhagic lesions or bleeding. Pneumonia , myocarditis, pericarditis, orchitis, hepatitis,

ulcerative gastritis, glomerulonephritis, and arthritis , Reye syndrome.

Nervous system damage: encephalitis, cerebellar ataxia, nystagmus, and tremor.

Therapy

Symptomatic therapy

Antivirals (acyclovir, famciclovir, or valacyclovir )

are effective in preventing severe complications

the routine oral administration of acyclovir is not

recommended in healthy children because of the

marginal therapeutic benefit, the lack of difference in

complications, and the cost of acyclovir treatment.

Prevention

Vaccine a live attenuated varicella vaccine is recommended as

a single dose for children at age 12 to 15 months, and repeated at 4-6years old.

post exposure prophylaxis immune suppression, perinatal neonate whose mother

suffering from chicken pox passive immunity: Immune globulin, within 10 day of ex

posure.

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