Exanthemas in

infectious diseases

Dr. Fauziah Mohamad Idris

Dept. of Medical Microbiology
& Parasitology
 What is an exanthem?
 A cutaneous eruption due to the systemic
effects of a microorganism on the skin
 Pathogenesis
– Multiplication in the skin
– Release of toxins that act on skin structures
– Evoking an inflammatory response involving phagocytes
– Via effects on vasculature, including vaso-occlusion and
necrosis and/or vasodilatation with oedema and hyperemia
 For many eruptions, several mechanisms can
play a role
 Morphologic Colour

types –Skin coloured

– Macules –Hyperpigmented
– Papules –Hypopigmented
– –Redness
Plaques
–Others
– Nodules
– Vesicles  Presence of
– Bullae haemorrhage
– Pustules – Petechiae
– Purpura
– Ecchymoses

 Absence of
haemorrhage
Causative organisms

Numerous
 Viruses
 Bacteria
 Fungi (disseminated)
 Protozoa (malaria)

Non-infectious causes of rash, esp.

drug reactions, should be considered
in any patient presenting with
rashes
Key ingredients in arriving
at a correct aetiological
diagnosis

 Distribution of the rash

 Pattern of progression
 Timing of the development of
rash (relative to onset of illness
and fever)
Measles (rubeola)
 Caused by measles virus (MV)
– Genus Morbillivirus
– Family Paramyxoviridae
– Only one serotype
 Incubation period: 8 to 12 days (generally)
 Prodrome
– fever, cough, coryza, and conjunctivitis
– Koplik’s spot on buccal mucosa (small irregular
bright red spots, minute bluish-white speck at
center)
 Followed by rash – starts on the head,
spread downwards; maculopapules
Schematic diagram of the clinical course of a typical case of
measles
Measles (rubeola)
 Occurs throughout the world

 MV infections in nonimmune individuals are

almost always symptomatic

 Newborns are the main source of new

susceptibles (i.e. when passively acquired
maternal antibody disappears)

 In endemic areas,
– epidemic occur at regular intervals
(with shorter interval in populations with high
birth rates)
Incidence, age of patient, and
severity of infection
vary strikingly
in different geographic areas
Incidence
In very isolated areas, in which whole populations are
susceptible, rapid spread through the entire
population, irrespective of age (attack rate ~100%)

Age of patients
Average age of infection 4-6 years
But in developing countries, almost all children are
infected before the age of 2 years
 Overcrowding
 Early loss of maternal antibodies (many infants
infected between 4 and 6 months of age)
Severity of infection
In developing countries:
 Complication rates as high as 80%
 Case fatality rate >15-20%
Early age of infection
Increased intensity of exposure and inoculum size
Rapid loss of maternal antibodies
Vitamin A deficiency
Prior or concurrent infection with other pathogens
Depressed cell-mediated immune responses secondary to
malnutrition
Transmission
 Large droplets (face-to-face exposure)****
 Airborne transmission**
 Indirect transmission (fomites)*
 Transplacental transmission
(prematurity/congenital measles)

Highly infectious
(secondary attack rate >90% in
susceptibles)
MV replication
• MV proliferates locally in respiratory
mucosa
• Spreads to draining lymph nodes
PRIMARY VIREMIA SECONDARY VIREMIA
 Disseminates to tissue
 Enter bloodstream (in
throughout body (skin,
infected leucocytes) conjunctivae, oropharynx,
 Disseminates respiratory mucosa, lungs,
throughout genital mucosa, kidneys,
reticuloendothelial gastrointestinal tract, liver)
system  (+ development of host
immune response)

Prodromal signs & symptoms

Duration of measles
infectiousness
 Latter part of incubation period
 During prodrome
 First 2 to 3 days of the rash

 Natural measles induces lifelong immunity

to disease
– Reinfection cause only limited virus replication –
almost always asymptomatic & non-infectious
Natural history of measles infection
Measles virus-induced
immunosuppression
 Major cause of secondary
infections that account for most
of the morbidity and mortality of
measles
 Prolonged dysregulation of cell-
mediated immunity (may persist
>1 year after MV infection)
Complications
 Pneumonia (60% of measles-associated death)
– Bacteria superinfection (esp. those younger
than 5 years old)
– Measles pneumonia (majority in adults)
 Otitis media, osteomyelitis, furunculosis &
other bacteria infections
 Diarrhoea (30 to 60% of children and adults
with measles; frequently associated with
secondary bacterial or protozoal infection in
developing countries)
 Croup (laryngotracheobronchitis)
 Keratitis
 Encephalitis
Measles encephalitis
 Acute postinfectious measles encephalomyelitis (acute
disseminated encephalomyelitis [ADEM])
 Most common neurologic complication of measles (1:1000)
 Typically abrupt onset
 First week after onset of rash (autoimmune disease – associated with
immune response to myelin basic protein)
 Subacute sclerosing panencepahlitis (SSPE)
 Rare; delayed complication (6 to 8 years after case of measles; death
within 1 to 3 years after onset in most cases)
 Insidious onset; pathogenesis unclear (MV mutants – persistent infection)
 Subacute measles encephalitis
(measles inclusion body encephalitis [MIBE])
 Progressive, generally fatal
 Occurs exclusively in immunocompromised patients
 ?mutant virus
 Rash
ADEM

MIBE
Virus
infection SSPE

Days Months Years

Timing of neurologic complications of measles

Vaccination has markedly
reduced worldwide incidence
(esp. in developed countries)
Laboratory diagnosis
 Serology
– Specific IgM (ELISA)
– Fourfold rise in antibody titer (HI, Nt tests)
 Antigen detection (in epithelial cells)
– Respiratory secretions
– Urine
 Isolation and identification of virus
– Nasopharyngeal swab
– Conjunctival swab
– Blood samples
– Respiratory secretions
– Urine
Treatment, prevention
& control
 Vitamin A treatment in developing
countries - decreased mortality and
morbidity
 Antiviral – none of proven benefit
 Attenuated live measles virus vaccine
– Monovalent form
– In combination with rubella vaccine (MR)
– In combination with rubella and mumps
vaccines (MMR)
 Rubella
 Caused by rubella virus
– Genus Rubivirus
– Family Togaviridae
 Mild, self-limited illness
– Affects children and young adults
 Infection in early pregnancy may result in serious abnormalities
of the fetus – congenital rubella syndrome

 Fever
– viremia after 7-9 days after infection
 Rash (morbilliform)
– develop on day 13-15 after infection (immunologic basis)
– Starts on the face, extends over the trunk and extremities (3
days)
 Lymphadenopathy
Fever (associated with viremia
after 7-9 days after infection)

Rash (morbilliform)
- develop on day 13-15 after
infection (immunologic basis)
- starts on the face, extends
over the trunk and extremities
(3 days)

Lymphadenopathy
Virus Blood
present Throat

Rash
Antibody
titer

r
te

s
of se af
Incubation period

th

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on ys

on

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Natural history of primary rubella infection M
 Chickenpox
Smallpox

Rubella
Congenital rubella
syndrome
Clinical features grouped in three broad
categories:
1. Transient effect in infants
2. Permanent manifestations that may be apparent at birth
or become recognized during the first year
3. Developmental abnormalities that appear and progress
during childhood and adolescence

Classic triad – cataracts, cardiac abnormalities, and deafness

Other symptoms – growth retardation, rash,
hepatosplenomegaly, jaundice, meningoencephalitis
Lab. diagnosis
 Serology
– Rubella specific IgM (ELISA)
– Rise in antibody titer (HI test)
– Specific IgG (ELISA) – evidence of
immunity

 Isolation & identification of virus

– Nasopharyngeal swab
– Throat swab
Varicella (chickenpox)
 Caused by varicella-zoster virus (VZV)
 Subclinical varicella ~5%
 Fever
 Rash
– Generalized
– Pruritic
– >trunk and head
– Successive fresh vesicles appear in crops
over 1 to 2 days
 first on trunk, then face, limbs
 all stages seen at one time – macules, papules,
vesicles, & crusts
 Self-limited (rash lasts about 5 days)
 Adults more likely to develop more severe
infections (presumably due to lower CMI
response to VZV) – > skin lesions, >primary
viral pneumonia
Transmission
 Spread by airborne route
– From skin
– From respiratory tract
– Both
 Spread by fomites does not occur

Highly communicable disease

Complications
 Bacterial superinfection of skin, lungs, or
bones
 CNS – transient cerebellar ataxia,
encephalitis, meningitis, transverse
myelitis

Maybe severe and fatal in immuno-

compromised patients (with deficiencies
in CMI)
– progressive varicella (large, umbilicated,
haemorrhagic)
– primary varicella pneumonia
– DIC
Lab. diagnosis
 Detection of virus-specific antigens
– Skin scrapings
 Virus isolation & identification
– Vesicle fluid
 Serologic tests
– VZV specific IgM
– Rise in VZV antibody titer
Treatment &
Prevention
 Acyclovir, valacyclovir, famciclovir, foscarnet
 Passive immunization against varicella with
VZIG
– For prevention of severe varicella in those at high
risk for severe disease
 Exposed immunocompromised children
 Newborns whose mothers have active varicella at the time
of delivery
 Live attenuated varicella vaccine – highly
effective – for healthy children and adults who
are susceptible to varicella
Human parvovirus B19
Erythema infectiosum (fifth disease)
– 3-stage rash
 Malar erythematous rash (slapped cheek)

 Reticulated or lacelike rash on trunk and

extremities
 Rash remit and recur with stress, exercise,
sunlight or bathing
– Onset of rash 1-4 days of fever (usually afebrile)
– Rashes disappears within 1-2 weeks
Human parvovirus B19
(continued)

Transient aplastic crisis

 Lytic infection of red cells precursors

Chronic anemia in patients with abnormal

immune systems
 Chronic infection leading to chronic
hypoplasia or aplasia of the erythroid
series in bone marrow
Hydrops fetalis
 Vertical transmission
 High-output congestive cardiac failure
(infection of expanding red cell volume;
infection of fetal myocardial cells)
Human herpes virus 6
(HHV-6)
 Exanthem subitum (roseola
infantum)
– Common disease among infants
– High fever
– Rash
 appearance coincides with subsidence of
fever
 Appears on trunk and face, spreads to
lower extremities
Human herpesvirus 6 (HHV-6)

Exanthem subitum (roseola

infantum)
– Common disease among infants
– High fever
– Rash
 appearance coincides with subsidence of
fever
 Appears on trunk and face, spreads to
lower extremities