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Received 2016 October 25; Revised 2017 March 07; Accepted 2017 March 13.
Abstract
Context: Many diseases caused by viral agents are associated with fever and cutaneous manifestations. Viral exanthema is a
widespread nonspecific skin rash, commonly characterized by generalized eruption of erythematous macules and papular lesions.
Although these rashes are mostly benign and self-limited, some may be serious and life-threatening. Differentiation between severe
and benign types is clinically important and life-saving.
Evidence Acquisition: In this narrative review, electronic databases, including Google Scholar, Science Direct, PubMed (including
Medline), Web of Science, Scientific Information Database, and Scopus, were searched. We conducted a narrative review of papers
published on pediatric viral exanthema during 2000 - 2016. The used keywords included “viral exanthema”, “fever”, and “skin rash”.
Articles on skin rash, caused by drug reactions or nonviral exanthema, were excluded.
Results: Different viral agents can cause different types of skin reactions. Cutaneous manifestations and skin rashes can be cate-
gorized, based on the form of the rash (macular, papular, vesicular, blistery, petechial, and purpuric) or the general term, which
denotes illnesses such as measles-like morbilliform rash, rubella or rubelliform rash, and scarlatiniform rash, a scarlet-fever like
infection.
Conclusions: Based on the findings, a systematic approach relying on accurate history-taking and analysis of epidemiological cues
and rash characteristics is of great significance.
Keywords: Viral Exanthema, Viral Rash, Exanthema, Viral Rash, Children, Infant
Copyright © 2017, Journal of Pediatrics Review. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0
International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the
original work is properly cited.
Saffar MJ et al.
were included. On the other hand, articles concerning skin age, season, geographical location, exposure, incubation
rashes, caused by drug reactions and nonviral exanthema, period, contact with animals/insects, history of immuniza-
were excluded. tion or prior diseases, immune system status, and medica-
tion use are more helpful in distinguishing viral infections
than exanthema itself.
3. Results
rubella syndrome.
Congenital rubella occurs when an unvaccinated preg- Primary infection with varicella zoster virus persists in
nant woman is infected during the first few weeks of ges- the body for a lifetime. Reactivation of the virus, as a re-
tation and the virus is transmitted to the fetus. Birth de- sult of diminished T-cell immunity (due to advanced age,
fects occur most commonly following infection during the immunosuppressant therapy, malignancy, and sometimes
first 16 weeks of pregnancy. Congenital rubella syndrome no obvious cause), leads to herpes zoster. Herpes zoster be-
is characterized by cataract, glaucoma, deafness, congen- gins with prodromal pruritus, tingling, tenderness, hyper-
ital heart disease, and central nervous system abnormali- esthesia, and/or intense pain in more than 90% of patients.
ties (ie, microcephaly and hydrocephalus) (15). These symptoms occasionally occur without subsequent
skin lesions, a phenomenon referred to as “zoster sine her-
3.3.3. Varicella pete”. However, most patients develop painful eruption
Varicella, also known as chickenpox, is caused by the of grouped vesicles on an erythematous base with a der-
varicella-zoster virus. It is the clinical manifestation of pri- matomal distribution.
mary infection with varicella zoster virus and is mainly a Herpes zoster usually resolves without sequelae in chil-
pediatric disease (16). Studies on unvaccinated cases in- dren and young adults with intact immune systems. How-
dicate that nearly 90% of individuals naturally become ever, pain, cutaneous lesions, and complications associ-
infected by 16 years of age. The disease is a vaccine- ated with herpes zoster become more severe with advanc-
preventable infection, and 2 doses of vaccine can lead to ing age and compromised immunity. The most common
complication is postherpetic neuralgia, which is character- Arthropathy is symmetric and polyarticular, involving
ized by dysesthetic pain (a burning or stabbing sensation the knees, fingers, and other joints. The characteristic rash
and allodynia) and persists after skin lesions have healed. in children is deep facial erythema (slapped cheek syn-
This condition affects 10% - 20% of all herpes zoster pa- drome) with perioral pallor. The symmetric red macular
tients, and its incidence and severity increase with age (18). skin rash extends from the trunk (proximal end of the ex-
tremities), is clear in the center, and progresses peripher-
3.3.4. Hand-Foot-Mouth Disease (HFMD) ally, with a lace-like reticulated appearance involving the
HFMD typically occurs in young children during sum- trunk, arms, buttocks, and thighs. The rash can wax and
mer and fall. It is highly contagious, and the most common wane with environmental changes, such as low and high
pathogen is coxsackievirus A16. Less common causative temperature for weeks to months.
agents include coxsackieviruses A2, A5, A9, A10, B2, B3, and In addition, other types of skin rash, such as rubel-
B5, as well as enterovirus 71 (19). Transmission is predom- liform rash, scarlatiniform rash, and papular-purpuric
inantly through the fecal-oral route. Exanthema is pre- glove-and-sock syndrome with pruritus may occur. Ery-
ceded by a prodromal stage (lasting 2 - 4 days) and is asso- thema infectiosum is characteristic in children, while in
ciated with fever, loss of appetite, sore throat, and abdomi- adults, the disease should be confirmed by specific IgM an-
nal pain. It is characterized by large (2 - 8 mm), oval, and tibodies. When diagnostic confirmation of B19 infection is
gray blisters on the dorsal surface of the fingers and the indicated, detection of serum anti-Bl9 IgM antibody is the
palmoplantar surface. preferred method; in fact, its presence indicates infection
Painful aphthous-like erosions on the oral mucous over the past 2 - 4 months. Nucleic acid hybridization and
membranes (palate, tongue, and cheeks) characterize polymerase chain reaction assay are especially useful for
enanthema (Figure 2). It should be noted that exanthema diagnosing infection in immunocompromised hosts (18).
is not always present at all sites of predilection (incom-
3.3.6. Epstein-Barr Virus Infection (EBV)
plete forms) and can also affect other regions, such as the
thighs. Recovery may be expected after 5 - 10 days (20-22). Infectious mononucleosis (IM) is the most common
The rash distribution in classical cases helps distinguish it presentation of EBV infection, which classically manifests
from other vesiculobullous diseases, such as herpetic in- as fever, exudative tonsillopharyngitis with petechiae, cer-
fection, herpes zoster, and chickenpox. vical lymphadenopathy, and atypical lymphocytosis. The
spectrum of disease is wide, ranging from asymptomatic
infection, unrecognized upper respiratory tract infection
in infants and young children, classic IM, IM with gener-
alized lymphadenopathy, hepatosplenomegaly, and even
complicated fatal infections.
In 3% - 15% of IM cases, a red maculopapular rash can de-
velop centrally within 3 - 5 days following the onset of the
disease. However, in more than 90% of patients with IM,
an erythematous maculopapular skin rash may develop on
the face, trunk, and extremities 5 - 10 days after treatment
with penicillin (eg, penicillin and amoxicillin); the rash
Figure 2. Hand-Foot-Mouth Disease Characterized by Oval, Gray Blisters with Painful may be pruritic mostly in adults rather than children. In-
Aphthous-Like Erosions
fection can be diagnosed serologically by positive IgM anti-
body against viral-capsid antigen (23). It may be even con-
fused with streptococcal pharyngitis or scarlet fever.
3.3.5. Parvovirus B19 Infection
This type of infection is most often known as erythema 3.3.7. Molluscum Contagiosum (MC)
infectiosum or fifth disease. In infants and children, it MC is the only remaining poxvirus infection to specifi-
is characterized by a distinctive rash, which may be pre- cally afflict humans. This disorder is caused by the MC virus
ceded by mild systemic or upper respiratory tract symp- (MCV), a member of the Molluscipox genus of Poxviridae
toms, including mild fever, malaise, headache, myalgia, viruses. Two molecular subtypes of the virus, ie, MCVI and
and arthralgia (7 - 10 days before exanthema eruption). In MCVII, can result in indistinguishable skin lesions. In gen-
older children, adolescents, and adults, especially women, eral, MC is a common, self-limited condition in children.
arthritis is more common, while skin rash is less promi- MC lesions are firm and umbilicated with pearly
nent and distinctive. papules and a waxy surface. They can occur anywhere on
the skin surface but are most common in skin folds (eg, ax- 3.3.9. Crimean-Congo Haemorrhagic Fever (CCHF)
illae and neck) on the lateral trunk, thighs, and genital re- CCHF is a serious and potentially fatal viral disease,
gion. Facial lesions can also occur and are often distressing which often has hemorrhagic manifestations. This dis-
for the patients. Also, widespread, large, and occasionally ease is a tick-borne viral infection, reported in many parts
deforming lesions may be seen in the setting of immuno- of the world including Iran. The virus is maintained
suppression, particularly AIDS. The associated molluscum through a tick-vertebrate-tick transmission cycle. The typ-
dermatitis is common, especially in children with atopic ical zoonotic hosts seem to be small mammals, including
dermatitis (24). sheep and goats.
The overt symptomatic disease is known to occur only
in humans. Humans are infected through tick bites or
3.3.8. Human Papillomavirus (HPV) Infection
contact with tissue, blood, or milk of infected animals or
HPV infects epithelial cells in the skin and mucous
humans. Since infected animals are asymptomatic, most
membranes. The most common clinical manifestation of
human cases are reported among farmers. Also, several
this virus is wart (verrucae). There are more than 150 dif-
outbreaks of CCHF have been reported among healthcare
ferent HPV subtypes, each with a tendency to a particular
workers, hospital staff, and laboratory technicians.
part of the body. For instance, the most common warts on
The incubation period seems to be 3 - 7 days. The pre-
the hands and feet are caused by HPV types 1, 2, 4, 27, and
hemorrhagic phase suddenly begins with high fever, gen-
57.
eral toxicity, flushing, myalgia, nausea, vomiting, and diar-
Warts have various forms, including common warts rhea, associated with conjunctival injection. After few days
(verruca vulgaris), flat warts, myrmecia, plantar warts, co- (mostly 3 days), the hemorrhagic phase begins and contin-
alesced mosaic warts, filiform warts, periungual warts, ues for 2 - 3 days. In this phase, petechia, large hematoma,
anogenital warts (venereal or condyloma acuminata), oral nasal bleeding, hematuria, and bleeding of the gingiva,
warts, and respiratory papillomas. Palmar and plantar gastrointestinal tract, vagina, and lung may occur. If the
warts are lesions described as rough papules on the palms, patient survives the hemorrhagic phase, a slow convales-
soles, and lateral sides of the hands and feet with slight cen- cent phase begins. Fatality is high, but early treatment
tral depression. with ribavirin may improve the outcomes (27).
Cutaneous warts are caused by a small group of specific
HPV types, with an overall prevalence of 20% in school chil-
3.3.10. Other Exanthematous Diseases
dren and a decline with increasing age. Patients residing
There are a number of viruses which cause exanthema
in larger households often report an infected cohabitant,
and are associated with respiratory or intestinal infections.
supporting person-to-person transmission. The majority
They primarily include nonpolio enteroviruses (coxsackie,
of warts regress spontaneously within 1 - 2 years. Reinfec-
ECHO, and new types of enterovirus) in the summer, as
tion with the same HPV type is uncommon after clearance,
well as rhinovirus, adenovirus, parainfluenza virus, respi-
suggesting the development of protective type-specific im-
ratory syncytial virus, and influenza virus in cold months.
munity.
Nonspecific exanthema is usually maculopapular. Also,
Common warts not only can cause inconvenience, anx-
enterovirus-associated exanthema tends towards the for-
iety and reduced quality of life among patients (due to
mation of papulovesicles resembling varicella, but lack the
persistence and pain), but also can be a therapeutic chal-
classic polymorphic appearance and rarely affect the scalp
lenge for clinicians; therefore, analysis of treatment op-
or oral mucosa; the specific exanthema in HFMD is an ex-
tions seems necessary. Although warts are self-limited in
ception. The main characteristics of some viral infections,
nature and can disappear after a few months, they may re-
accompanied by cutaneous manifestations, are presented
main for years and have recurrences (25, 26).
in Table 1.
A subset of HPVs, designated as high-risk (most often
HPV 16 - 18), is now recognized as the primary etiological
agent for cervical cancer and the associated precursor le- 4. Conclusions
sions (a subset of malignancies in other anogenital sites or
upper aerodigestive tract and squamous cell cancer of the Fever is a common symptom among patients with vi-
digits in rare cases). In contrast, infection with common ral exanthema. In the initial evaluation of febrile children
cutaneous HPV types (eg, types 1, 2, 4, and 27) is not thought with rash, proper history-taking and careful clinical exam-
to have an oncogenic potential. In immunocompromised ination are preferred to the sole use of laboratory tests, the
patients, HPV infection tends to persist and result in an in- results of which may not be immediately available. Certain
creased risk of anogenital neoplasia. exanthema rashes have distinct patterns and prodromal
Table 1. The Main Characteristics, Clinical Presentations, and Types of Rash in Some Viral Infections
symptoms (before rash eruption), which aid in incriminat- 10. Saffar MJ, Amiri-Alreza M, Baba-Mahmoodi F, Saffar H. Measles
ing the causative virus. However, in many cases, an accu- epidemiology in Mazandaran province, Iran, 2000-2002. Trop
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