Evaluating the Febrile Patient with a

Rash
HARRY D. MCKINNON, JR., MAJ, MC, USA, and
THOMAS HOWARD, COL, MC, USA
Dewitt Army Community Hospital, Fort Belvoir, Virginia

The differential diagnosis for febrile patients with a rash is extensive. Diseases that present with
fever and rash are usually classified according to the morphology of the primary lesion. Rashes
can be categorized as maculopapular (centrally and peripherally distributed), petechial, diffusely
erythematous with desquamation, vesiculobullous-pustular and nodular. Potential causes include
viruses, bacteria, spirochetes, rickettsiae, medications and rheumatologic diseases. A thorough
history and a careful physical examination are essential to making a correct diagnosis. Although
laboratory studies can be useful in confirming the diagnosis, test results often are not available
immediately. Because the severity of these illnesses can vary from minor (roseola) to life-
threatening (meningococcemia), the family physician must make prompt management decisions
regarding empiric therapy. Hospitalization, isolation and antimicrobial therapy often must be
considered when a patient presents with fever and a rash. (Am Fam Physician 2000;62:804-16.)

Evaluating the patient who presents with fever and a rash can be challenging because
the differential diagnosis is extensive and includes minor and life-threatening illnesses. In
addition, the clinical picture can vary considerably, and the family physician may need to
quickly decide about initiating empiric therapy or isolation. This article reviews common
diagnoses for fever and a rash and suggests a logical approach to obtaining the correct
diagnosis.1-3
A history of recent travel,
History
woodland or animal exposure,
drug ingestion or contact with ill
A detailed history can be quite helpful in
persons should be noted when
identifying the cause of fever and a rash. A history
the family physician evaluates
of recent travel, woodland or animal exposure, drug
a patient who has fever and a
ingestion or contact with ill persons should be
rash.
noted. The time of year can be a clue to certain
diagnoses.2-4

A complete medical history can help to determine whether the patient is at increased risk
for specific conditions associated with valvular heart disease, sexually transmitted
diseases or immunosuppression from chemotherapy. Immune status is particularly
important because many of the diseases that result in fever and a rash present differently
in immunocompromised patients.2-4

Details about the rash should include site of onset, rate and direction of spread, presence
or absence of pruritus, and temporal relationship of rash and fever.2-5 It is also important
to know whether any topical or oral therapies have been attempted.
Physical Examination

A basic understanding of the various types of rashes is essential in making an accurate

assessment and determining the severity and acuteness of the patient's illness. Brief
descriptions of common primary skin lesions are presented in Table 1.1,6

The physician should identify the primary lesion but also note the presence of secondary
lesions. Important features include the distribution, configuration and arrangement of the
lesions.2

In addition to evaluating the patient's vital signs and general appearance, the physician
should look for the following: signs of toxicity, adenopathy, oral, genital or conjunctival
lesions, hepatosplenomegaly, evidence of excoriations or tenderness, and signs of nuchal
rigidity or neurologic dysfunction.2,4

TABLE 1
Common Primary Skin Lesions
Lesion
type Description
Macule Circumscribed area of change in normal skin color, with no skin elevation or
depression; may be any size
Papule Solid, raised lesion up to 0.5 cm in greatest diameter
Nodule Similar to papule but located deeper in the dermis or subcutaneous tissue;
differentiated from papule by palpability and depth, rather than size
Plaque Elevation of skin occupying a relatively large area in relation to height; often
formed by confluence of papules
Pustule Circumscribed elevation of skin containing purulent fluid of variable character
(i.e., fluid may be white, yellow, greenish or hemorrhagic)
Vesicle Circumscribed, elevated, fluid-containing lesion less than 0.5 cm in greatest
diameter; may be intraepidermal or subepidermal in origin
Bulla Same as vesicle, except lesion is more than 0.5 cm in greatest diameter
Information from Fitzpatrick TB, et al. Color atlas and synopsis of clinical dermatology: common and
serious diseases. 3d ed. New York: McGraw-Hill, Health Professions Division, 1997, and Habif TP.
Clinical dermatology: a color guide to diagnosis and therapy. 3d ed. St. Louis: Mosby, 1996.

Laboratory Data

Laboratory data are not usually available during the initial evaluation. The complete
blood count with differential, an erythrocyte sedimentation rate, a chemistry panel, liver
function tests, and blood and urine cultures may prove useful in identifying organisms or
disease processes.1
Aspirates, scrapings and pustular fluid may be obtained for Gram staining and culture.
When a herpes simplex virus infection is suspected, a Tzanck test may be performed by
unroofing a lesion and taking a scraping of the lesion base. Biopsy samples should be
obtained from nonhealing or persistent purpuric lesions. Biopsy of inflammatory dermal
nodules and ulcers should also be considered.1

Specific diagnoses that may be confirmed histologically include Rocky Mountain spotted
fever, herpetic infections, systemic lupus erythematosus, erythema multiforme, allergic
vasculitis, secondary syphilis and deep fungal infections.1,6,7

Although serologic tests are not helpful in the acute setting, they can be used to confirm
or support the diagnosis of conditions such as systemic lupus erythematosus, syphilis,
rheumatoid arthritis and human immunodeficiency virus infection.1,6,7

Diseases that present with fever and rash are summarized in Table 21,2 and discussed by
rash type in the following sections.

TABLE 2
Diseases Presenting with Fever and Rash
Description Epidemiolo Diagnostic Basis for
Disease Etiology of rash gy clues diagnosis
Rubeola Measles Macular- Most Prodrome Serology
virus papular rash common in consisting of
that may children 5 to symptoms of
become 9 years of upper
confluent; age, respiratory tract
begins on nonimmune infection,
face, neck persons coryza, bark-
and shoulders like
and spreads cough,malaise,
centrifugally photophobia
and inferiorly; and fever;
fades in 4 to 6 Koplik's spots
days (prodromal
stage);
development of
exanthem on
fourth febrile
day; late winter
through early
spring
Rubella Rubella virus Pink macules Young Prodrome Serology
and papules adults, uncommon,
that develop nonimmune especially in
on forehead persons children;
and spread petechiae on
inferiorly and soft palate
 to extremities (Forschheimer'
within one s spots); in
day; fading of adults:
macules and anorexia,
papules in malaise,
reverse order conjunctivitis,
by third day headache and
symptoms of
mild upper
respiratory
infection
Erythema Human Begins as Children 3 Can present as Serology
infectiosum parvovirus classic bright- to 12 years rheumatic
(fifth disease) B19 red facial rash of age syndrome in
("slapped adults;
cheek") and prodrome of
progresses to fever, anorexia;
lacy reticular rash typically
rash; may wax beginning after
and wane for resolution of
6 to 8 weeks fever
Roseola Human Diffuse Children 6 Fever lasting 3 Clinical
herpes-virus maculopapula months to 3 to 4 days, findings,serol
6 r eruption, years of age followed within ogy
usually 2 to 3 days by
sparing face the rash, which
resolves
spontaneously
in several days;
almost always
a self-limited
benign disease;
temporal
relationship of
fever followed
by rash is
helpful in
making the
diagnosis
Lyme disease Borrelia Macule or All ages at History of tick Clinical
burgdorferi papule at site risk for tick exposure; findings,
of tick bite, exposure in secondary serology,
progressing to endemic erythematous, polymerase
pathognomoni areas macular chain reaction
c erythema lesions; test
migrans Borrelia
lymphocytoma;
highest
incidence: May
through
September
Erythema Idiopathic in Dull-red Adults 20 to Major and Clinical
multiforme 50 percent of macules 30 years of minor forms; findings
cases (see developing age; men major form
Table 3) into papules affected always with
with central more often mucous
vesicles or than women membrane
bullae; involvement
common on and usually the
dorsa of result of drug
hands, palms, reaction; minor
soles, arms, form often
knees, penis associated with
and vulva; herpes simplex
often bilateral outbreak; rarely
and life-threatening
symmetric
Secondary Treponema Various Adolescents Develops 2 to Dark-field
syphilis pallidum presentations; and adults 10 weeks after examination,
brownish- red 15 to 49 primarychancre serology
or pink years of ; presents with
macules and age; or without
papules; females fever; may
generalized affected have
eruption or more often generalized
localized than males lymphadenopat
eruption on hy and
head, neck, splenomegaly;
palms or may have
soles; recurrent
condyloma eruptions with
lata common symptom-free
periods
Meningococce Neisseria Variety of Highest Acutely ill Often, clinical
mia (acute) meningitidis lesions but, incidence in patient; high findings;
characteristica children 6 fever, blood cultures
lly, petechial months to 1 tachypnea,
lesions year of age tachycardia,
distributed on mild
the trunk and hypotension;
extremities leukocytosis;
(although the meningitis
lesions can be develops in
located more than 50
anywhere); percent of
petechiae on patients
mucous
membranes
Meningococce N. Intermittent Same as for Fever, Blood
mia (chronic) meningitidis maculopapula acute form myalgias, cultures
r lesions, arthralgias,
often on a headache,
painful joint or anorexia; may
 pressure recur for weeks
point; may or months, with
have nodules average
on calves duration of 8
weeks; may
progress to
acute
meningococce
mia, meningitis
or endocarditis
Rocky Rickettsia Rash evolving Young Onset typically Clinical
Mountain rickettsii from pink adults with abrupt; fever, findings,
spotted fever macules to tick severe serology
red papules exposure; headache and
and finally to men myalgias are
petechiae; affected prominent; rash
rash more often appearing
beginning on than women around fourth
wrists and day of illness;
ankles and may have
spreading relative
centripetally; bradycardia
involvement of and leukopenia
palms and
soles late in
disease
Scarlet fever Beta- Punctate Children Acute infection Rapid strep
hemolytic erythema of tonsils or test, wound or
Streptococc beginning on skin; linear throat culture,
us pyogenes trunk and petechiae in antistrepto-
spreading to antecubital and lysin O titers
extremities, axillary folds
becoming (Pastia's sign);
confluent; rash appearing
flushed face 2 to 3 days
with perioral after infection;
pallor; rash initially, "white
fading in 4 to strawberry
5 days and tongue" but by
followed by fourth or fifth
desquamation day, "red
strawberry
tongue"
Toxic shock Staphylococ Diffuse All ages, but High fever, Clinical
syndrome cus aureus "sunburn" most hypotension criteria,
rash that common in and vaginal and
desquamates menstruatin involvement of wound
over 1 to 2 g females three or more cultures
weeks organ systems;
about 50
percent of
cases occurring
 in menstruating
women around
onset of
menses;
postoperative
patients at
increased risk;
condition out of
proportion to
wound
appearance
Kawasaki's Idiopathic Erythematous Children Winter and Specific
disease rash on hands less than 8 spring; high clinical criteria
and feet; years of fevers, cervical
morbilliform, age, with lymphadenopat
scarlatiniform peak hy, arthritis,
rash on trunk incidence at arthralgias,
and perineum; 1 year; boys cardiac
hyperemic lips affected involvement,
more often mucous
than girls membrane
involvement;
can be
complicated by
coronary artery
abnormalities in
20 to 25
percent of
cases
Chickenpox Varicella- Initially, 90 percent Prodrome Clinical
zoster virus papules, of cases in consisting of findings,
which evolve children headache, confirmed by
into vesicles less than 10 general aches, Tzanck test
("dewdrops on years of backache and
a rose petal") age; 5 malaise is
and eventually percent of typically absent
into pustules cases in in children;
and crusts; persons exposure
rash older than history; may
beginning on 15 years have all forms
face and of lesions at the
spreading same time;
inferiorly to vesicles
trunk and evolving to
extremities shallow
erosions
common on
mucous
membranes of
palate; may
also have
vesicles on
 nasal,
conjunctival,
gastrointestinal
tract and
genital mucosa
Herpes zoster Varicella- Begins as All ages, but Prodrome of Clinical
(shingles) zoster virus erythematous incidence unusual skin findings,
maculopapula increases sensations; confirmed by
r eruption, with age dermatomal Tzanck test
rapidly and pattern, with
evolves to immuno- lesions rarely
vesicles suppression crossing
midline; pain
often severe;
more common
in thoracic and
facial
dermatomes
Rickettsialpox Rickettsia Generalized All ages; Transmitted Serology
akari maculopapula urban from mice to
r-vesicular settings humans via
exanthem; mites;
possible formation of
involvement of papules 7 to 10
mucous days after initial
membranes; bite; typically,
no formation of a
involvement of black eschar
palms or soles over healing
lesion; febrile
phase
occurring 3 to 7
days after initial
lesion and
lasting up to a
week; self-
limited, usually
mild course
Erythema Various Bright-red Adolescents Thorough Clinical
nodosum causes (see nodules (3 to and young history and findings
Table 4) 20 cm in adults 15 to physical
diameter) 30 years of examination to
scattered age; identify known
bilaterally but females causes; throat
not affected culture for
symmetric; more often group A beta-
most than males hemolytic
frequently on streptococci;
lower legs but chest
also found on radiograph to
knees and rule out
arms; rarely sarcoidosis;
 found on face arthralgias
and neck; present in 50
lesions often percent of
tender and cases; fever
indurated and malaise
common
Adapted with permission from Kaye ET, Kaye KM. Fever and rash. In: Fauci AS, et al., eds. Harrison's
Principles of internal medicine. 14th ed. New York: McGraw-Hill, Health Professions Division, 1998:90-7,
with additional information from Fitzpatrick TB, et al. Color atlas and synopsis of clinical dermatology:
common and serious diseases. 3d ed. New York: McGraw-Hill, Health Professions Division, 1997.

Maculopapular Rashes

Maculopapular eruptions are most frequently seen in viral illnesses (Figure 1) and
immune-mediated syndromes. These eruptions can have many causes, including drug
reactions and bacterial infections. Infectious exanthems are common and are defined as
generalized cutaneous eruptions associated with a systemic infection. It is helpful to
consider centrally and peripherally distributed eruptions separately because each type has
its own differential diagnosis.2

Centrally Distributed Eruptions

Centrally distributed maculopapular eruptions are more common than peripheral
eruptions.2 These eruptions include rashes that begin centrally, first affecting the head and
neck, and then progress peripherally.

Viral Exanthems. Viral etiologies of rashes include rubeola, rubella, erythema

infectiosum and roseola.4

The exanthem of rubeola begins around the fourth febrile day, with discrete lesions that
become confluent as they spread from the hairline downward, sparing the palms and
soles. The exanthem typically lasts four to six days. The lesions fade gradually in order of
appearance, leaving a residual yellow-tan coloration or faint desquamation. Rubeola is
also distinguished by the presence of Koplik's spots in the oral mucosa.1,2

Rubella is similar to rubeola. However, it causes less severe symptoms, and its exanthem
characteristically has a shorter duration (two to three days).1,2
 FIGURE 1. Maculopapular rash in
a nonspecific viral exanthem.

FIGURE 2. Maculopapular rash of

erythema infectiosum (fifth
disease).

Erythema infectiosum, or fifth disease, is caused by human parvovirus B19. This disease
primarily affects children between three and 12 years of age, although it can present as a
rheumatic syndrome in adults. The prodrome may consist of fever, anorexia, sore throat
and abdominal pain. Once the fever resolves, the classic bright-red facial rash ("slapped
cheek") appears. Within several days, the exanthem progresses to a diffuse, lacy, reticular
rash that may wax and wane for six to eight weeks
(Figure 2). Human parvovirus B19 infection is of
Roseola is caused by human
particular concern in pregnant women because it
herpesvirus 6 and usually
has been associated with fetal hydrops and
occurs in children less than
subsequent fetal death.1,4,7,8
three years of age. A diffuse
maculopapular eruption
Roseola, or exanthema subitum, is caused by
appears after the resolution of
human herpesvirus 6. This disease occurs in
high fever; the face is usually
children less than three years of age. As in fifth
spared.
disease, the rash appears after the resolution of
several days of high fever. The diffuse
maculopapular eruption often spares the face and is
of short duration, typically fading within three days.7,8

Lyme Disease and Erythema Migrans. Lyme disease is the most commonly reported
vector-borne illness in the United States.7 It is caused by the spirochete Borrelia
burgdorferi, which is transmitted by the bite of a tick (Ixodes species). Endemic areas in
the United States include the northeastern, mid-Atlantic, north-central and far-western
regions.9

Erythema migrans, the pathognomonic rash, develops in

about 80 percent of patients with Lyme disease.6 This
enlarging, erythematous macular rash begins as a
macule or papule at the site of inoculation (Figure 3).
Systemic symptoms, including fever, chills, myalgias,
headaches and arthralgias, often accompany the rash.1,10

FIGURE 3. Erythema migrans on

upper arm in Lyme disease.
The rash is more common on the proximal extremities, in body creases and on the chest.
It enlarges over a period of days to weeks, reaching a maximum diameter of 3 to 68 cm
(median diameter: 15 cm).1,10

The primary lesion may show central clearing,

central necrosis, induration or vesiculation. Smaller
Borrelia lymphocytoma is a
secondary lesions may develop in up to 20 percent
painless bluish-red nodule that
of patients with Lyme disease and may indicate
may be seen in early Lyme
early hematogenous spread.10
disease. The lesion is usually
located on the earlobe, nipple
Borrelia lymphocytoma is a painless bluish-red
or scrotum.
nodule or plaque that may develop in early Lyme
disease. The lesion is usually located on the earlobe,
nipple or scrotum.9

Complications of untreated Lyme disease include carditis, neuroborreliosis, arthritis and

acrodermatitis chronica atrophicans.9

Drug-Related Eruptions. Drug reactions can present as any dermatologic morphology

and show no predilection for age, gender or race. Exanthematous eruptions most
commonly occur in association with the administration of penicillins or cephalosporins.
The rash usually appears within the first week after the offending drug is started and
typically resolves within days after the drug is discontinued. Drug-related reactions can
be difficult to distinguish from viral exanthems, but they may be more intensely
erythematous and pruritic.1,2,11

Peripheral Eruptions
Erythema Multiforme. The most common peripheral eruptive maculopapular rash,
erythema multiforme occurs more frequently in men than in women and most often
affects persons between 20 and 30 years of age. The rash, which can be recurrent, shows
a predilection for palms, soles, knees and elbows. Although erythema multiforme has a
number of known etiologies (Table 3),1,4,6 it is idiopathic in more than 50 percent of
affected patients.1,6

TABLE 3
Etiologies of Erythema Multiforme
Idiopathic (more than 50 percent of cases) Infectious causes
Herpes simplex virus
Radiation therapy Epstein-Barr virus
Adenovirus
Coxsackievirus B5
Medications
Vaccinia virus
Penicillin
Mycoplasma species
Sulfonamides
Chlamydia species
Phenytoin (Dilantin)
Salmonella typhi
Barbiturates
Yersinia species
 Mycobacterium tuberculosis
Phenylbutazone Histoplasma capsulatum
Coccidioides immitis
Information from Fitzpatrick TB, et al. Color atlas and synopsis of clinical dermatology: common and
serious diseases. 3d ed. New York: McGraw-Hill, Health Professions Division, 1997; Weber DI, Cohen
MS, Fine JD. The acutely ill patient with fever and rash. In: Mandell GL, Bennett JE, Dolin R, eds.
Mandell, Douglas, and Bennett's Principles and practice of infectious diseases. 5th ed. Philadelphia:
Churchill Livingstone, 1999:633-50; and Habif TP. Clinical dermatology: a color guide to diagnosis and
therapy. 3d ed. St. Louis: Mosby, 1996.

Erythema multiforme begins as a macular eruption (Figure 4). The dull-red lesions
advance from macules to papules, with prominence of characteristic target-shaped
lesions. Vesicles and bullae may develop in the center
of the papules. In many patients, the mucous
membranes of the mouth and lips are involved.1

The illness is classified as minor or major, depending

on severity. In erythema multiforme minor, bullae and
systemic symptoms are absent. The eruption is
typically confined to the extensor surfaces of
extremities and only rarely involves the mucous FIGURE 4. Erythema multiforme
membranes. Recurrent episodes of erythema associated with sulfa drug
multiforme minor usually precede an outbreak of administration.
herpes simplex by several days. [corrected]
Recurrences may be prevented with chronic acyclovir (Zovirax) therapy.1

Erythema multiforme major most often results from a drug reaction. Mucous membranes
are always involved. The eruption tends to become bullous and systemic symptoms,
including fever and prostration, are present. Eating may be complicated by cheilitis and
stomatitis, and micturition may be difficult because of balanitis and vulvitis.
Conjunctivitis may be severe and can lead to keratitis and ulceration. Lesions may also be
found in the pharynx, larynx and trachea. Rarely, erythema multiforme major can be life-
threatening and can progress to necrotizing tracheobronchitis, meningitis, blindness,
sepsis and renal tubular necrosis.1,4,6

Secondary Syphilis. The rash of secondary syphilis can be diffuse, with localized
eruptions often occurring on the head, neck, palms and soles. The lesions are typically
brownish-red or pink macules and papules, but they may be papulosquamous, pustular or
acneiform. The eruption usually occurs two to six months after the primary infection and
two to 10 weeks after the primary chancre.12

Patients often present with acute constitutional symptoms, and asymptomatic flat-topped
macules and papules (mucous patches) are commonly found on the oral and genital
mucosa. Classic condyloma lata may also be found in the perineum.1,6,12
Others. Meningococcemia, Rocky Mountain spotted fever and dengue fever--all
potentially life-threatening infections--may initially present with erythematous
maculopapular lesions before advancing to a petechial exanthem.3,13

Petechial Eruptions

Petechial rashes warrant immediate evaluation to Petechial rashes warrant

rule out severe, life-threatening illness. For proper immediate evaluation to rule
assessment of an acutely ill patient with a petechial out severe, life-threatening
rash, the physician must be familiar with the illness.
common infectious and noninfectious etiologies.
Prompt, accurate diagnosis and early treatment can
be life-saving in patients with meningococcemia, rickettsial infections and bacteremia.3,13

Meningococcemia
Meningococcal infections are a worldwide concern. These infections occur sporadically
or in epidemics, most commonly in the midwinter months.1 Seeding of Neisseria
meningitidis from the nasopharynx may result in acute meningococcal septicemia,
meningococcal meningitis or chronic meningococcemia. The risk of meningococcal
disease is highest in infants, asplenic patients,
alcoholics and patients with a complement deficiency
(especially C5 to C8).1

In some patients, the typical prodrome of cough,

headache, sore throat, nausea and vomiting may be of
short duration. Patients with acute meningococcemia
appear ill and usually present with a characteristic
petechial rash (Figure 5), a high, spiking fever,
tachypnea, tachycardia and mild hypotension. In the FIGURE 5. Petechiae in
early stages of disease, the rash may be meningococcemia.
maculopapular.14 Signs and symptoms of meningeal
irritation may be helpful, given that up to 88 percent1 of patients with meningococcemia
develop meningitis.1,13-15

Chronic meningococcemia is a rare condition. Patients may present with intermittent

rash, fever, arthritis and arthralgias occurring over a period of weeks to several months.
In some patients, the chronic form advances to acute meningococcemia.1 The rash may be
polymorphous, with maculopapular lesions usually located around a painful joint or
pressure point, nodules on the lower extremities and petechiae of variable size.1,4,7,13-15

Rocky Mountain Spotted Fever

Rocky Mountain spotted fever is the most common rickettsial disease in the United
States.16 It is caused by Rickettsia rickettsii, which is transmitted through a tick bite or
contact with tick feces or tissue juices.1
The disease occurs most often in young men between April and September.16 In the
United States, the areas with the highest prevalence of Rocky Mountain spotted fever are
Oklahoma and the southern Atlantic states.6

The prodrome may include malaise, chills, a feverish feeling, anorexia and irritability.
The onset of symptoms may be abrupt, with the predominant features being fever (94
percent), severe headache (86 percent), generalized myalgia (83 percent), shaking rigor,
photophobia, prostration and nausea. The diagnosis can be difficult when the onset is
gradual and no rash is present, as is the case in up to 20 percent of adults and 5 percent of
children with Rocky Mountain spotted fever.16
The rash of Rocky Mountain
When rash is present, it develops on approximately
spotted fever develops on
the fourth day of illness. Its appearance, combined
about the fourth day of illness
with the temporal evolution, is characteristic of
as small macules located on
Rocky Mountain spotted fever. The rash typically
the wrists and ankles. The
begins as pink macules, 2 to 6 mm in diameter,
lesions progress to papules
located on the wrists, forearms, ankles, palms and
and then to petechiae.
soles. Within six to 18 hours, the rash spreads
centrally to involve the arms, thighs, trunk and face.
In the ensuing one to three days, the lesions evolve
into deep-red papules. Within two to four days after onset of the rash, the lesions become
petechiae.1,4,7,13,16,17

Other Causes
Viral illnesses known to cause petechial rashes include coxsackievirus A9, echovirus 9,
Epstein-Barr virus and cytomegalovirus infections, atypical measles and viral
hemorrhagic fevers caused by arboviruses and arenaviruses. Coxsackievirus and
echovirus infections in children can produce severe illness and, at times, are difficult to
distinguish from meningococcemia.4

Included in the differential diagnosis of petechial rash are disseminated gonococcal

infections, bacteremia, staphylococcemia and thrombotic thrombocytopenic purpura.

Diffuse Erythema with Desquamation

Scarlet Fever
Scarlet fever provides the classic example of an erythematous rash with subsequent
desquamation. Most common between one and 10 years of age,18 scarlet fever usually
follows an acute infection of the tonsils or skin by group A beta-hemolytic streptococci
that produce an erythrogenic exotoxin.2 Patients may appear acutely ill and have fever,
sore throat, headache, chills, nausea and vomiting.1,18

The rash begins as finely punctate erythema on the superior trunk and face two to three
days after the onset of illness. The erythema quickly spreads to the extremities. When
present, petechiae in the antecubital and axillary skin folds (Pastia's lines) can be helpful
in making the diagnosis.1,2
Initially, the tongue may appear white, with red, swollen papillae (white strawberry
tongue), but by the fourth or fifth day, it becomes bright red (red strawberry tongue). The
oral mucosa may have punctate erythema or petechiae, and the tonsils may be acutely
infected.1

The exanthem varies in intensity. However, it usually fades in four to five days and is
followed by diffuse desquamation.1

The infection may be mild, and patients may present with only complaints of
desquamation. Rarely, the streptococcal
infection may produce a toxic-shocklike
picture that results in hypotension and
multisystem failure. Many of these
patients have a localized tissue infection
that progresses to necrotizing fasciitis,
which usually warrants immediate
surgical intervention.1,2

Toxic Shock Syndrome and Scalded

Skin Syndrome
Staphylococcus aureus is the organism
responsible for classic toxic shock FIGURE 6. Diffuse erythema in toxic shock
syndrome and scalded skin syndrome. syndrome.
Toxic shock syndrome can present with
hypotension, erythema, fever and multisystem dysfunction.3 Most cases of nonmenstrual
toxic shock syndrome occur in the postoperative setting.1

Several different staphylococcal exotoxins have been implicated. The syndrome may
result from infection, or it may occur because of simple colonization with S. aureus.3
Staphylococcal scalded skin syndrome occurs in infants, young children and adults with
immunosuppression or renal impairment.1

The rash is usually diffuse and can present as bullous impetigo, scarlatiniform lesions or
diffuse erythema (Figure 6). The mucous membranes are spared in most patients. During
the physical examination, the physician should attempt to elicit Nikolsky's sign (shearing
of the skin with gentle lateral pressure).1,3,4

Kawasaki's Disease
Kawasaki's disease, or mucocutaneous lymph node syndrome, is an acute febrile illness
that affects infants and young children (mean age: 2.6 years). The disease is uncommon
after the age of 12 years.6

In patients with Kawasaki's disease, fever begins abruptly, and the temperature is
typically higher than 40°C (104°F). The fever lasts five to 30 days (mean duration: 8.5
days) and does not respond to antibiotics and antipyretics.6,8
 TABLE 4
Etiologies of Erythema
Nodosum
Idiopathic (40 percent of cases)
The rash appears within three days of the Infectious causes
onset of fever and can vary in character. Beta-hemolytic streptococci
Frequently, the rash is scarlatiniform on the Yersinia species
trunk and erythematous on the palms and Hepatitis C virus
Mycobacterium species
soles, with subsequent distal desquamation. Chlamydia trachomatis
Mucous membrane involvement is common Coccidioides immitis
and includes hyperemic bulbar conjunctiva, Noninfectious causes
injected oropharynx, dry, cracked lips and a Medications
strawberry tongue.1,6 Sulfonamides
Oral contraceptives
Systemic lupus erythematosus
The physical examination may reveal Sarcoidosis
nonsuppurative cervical lymphadenopathy Ulcerative colitis
(more than 1.5 cm in diameter). Coronary Behçet's syndrome
artery abnormalities develop in 20 to 25 Pregnancy
percent of patients with Kawasaki's disease.19 Information from Fitzpatrick TB, et al. Color
atlas and synopsis of clinical dermatology:
Cardiovascular complications are the major common and serious diseases. 3d ed. New
cause of short-term and long-term morbidity York: McGraw-Hill, Health Professions
and mortality.1,6,8,19 Division, 1997, and Weber DI, Cohen MS,
Fine JD. The acutely ill patient with fever
Other Causes and rash. In: Mandell GL, Bennett JE, Dolin
R, eds. Mandell, Douglas, and Bennett's
Ehrlichiosis, a rickettsial-like infection, can Principles and practice of infectious diseases.
occasionally be associated with a clinical 5th ed. Philadelphia: Churchill Livingstone,
picture similar to toxic shock syndrome, 1999:633-50.
including diffuse erythema. Streptococcus
viridans bacteremia is another rare cause of
generalized erythema. Finally, enteroviral
infections, toxic epidermal necrolysis, graft-versus-host reaction, erythroderma and
generalized pustular psoriasis (von Zumbusch's psoriasis) may present with diffuse
erythema.1,3

Vesiculobullous-Pustular Eruptions

Varicella-Zoster Virus Infections

Varicella-zoster virus is the most infectious of the human herpesviruses. It is responsible
for varicella (chickenpox) and herpes zoster (shingles).20

Varicella. Primary infection with varicella-zoster virus results in chickenpox, a common

childhood illness. Its highest incidence is in late winter and spring.2 The disease is
typically more severe in adults and immunocompromised patients.1,6

The clinical presentation consists of rash,

fever and general malaise.2 A mild prodrome
lasting one to two days before appearance of
the rash is not uncommon. The rash typically
begins on the face, scalp or trunk and then
spreads to the extremities.8

FIGURE 7. Rash of varicella (chickenpox).

The lesions appear as erythematous macules and progress to papules with an edematous
base (Figure 7). The papules quickly evolve into vesicles, with each vesicle initially
having the appearance of "a dewdrop on a rose petal."1 The vesicles evolve into pustules,
which become umbilicated and subsequently crust over in the ensuing eight to 12 hours.
An enanthema may be noted, and vesicles may evolve to shallow erosions, primarily on
the palate. On physical examination, lesions in all stages may be present.1

Complications are unusual in immunocompetent patients. In children, the most common

complication is secondary bacterial infection of excoriated lesions.7

The central nervous system (CNS) is the most common site of extracutaneous
involvement in children. Cerebellar ataxia is the most frequently encountered syndrome.
Other possible CNS complications include encephalitis, meningitis, transverse myelitis
and, rarely, Reye's syndrome (especially subsequent to aspirin use). Varicella pneumonia
and encephalitis can be serious complications in adults. Additional rare complications in
children and adults include myocarditis, corneal lesions, nephritis, arthritis, bleeding
diatheses, acute glomerulonephritis and
hepatitis.1,2,7,21 The most common location for
herpes zoster is the chest,
Herpes Zoster. After the primary infection, the followed by the face. Only a
varicella-zoster virus lies dormant in the dorsal root single dermatome is usually
ganglia. Herpes zoster is caused by reactivation of affected, and the lesions rarely
the virus.20 Although shingles can occur at any age, cross the midline.
its incidence increases significantly with age and in
immunocompromised patients. An estimated 10 to
20 percent of the general U.S. population will have herpes zoster at some time in life.20

The characteristic vesicular rash of herpes zoster usually affects a single dermatome and
rarely crosses the midline (Figure 8). The most common locations are the chest
(approximately 50 percent of cases) and the face (approximately 20 percent of cases).20 A
prodrome of unusual skin sensations may evolve into pain, burning and paresthesias,
which precede the rash by two to three days.

The rash begins as an erythematous maculopapular

eruption that rapidly evolves to a vesicular rash.21 In
about 5 percent of patients, the rash may be
accompanied by headache, malaise and fever.1 Drying
of the lesions with crust formation generally occurs in
seven to 10 days, and the lesions usually resolve in 14 to
21 days.20

Pain is the most debilitating feature of herpes zoster,

and postherpetic neuralgia is the most common long-
term complication. Postherpetic neuralgia is uncommon
in young patients but may affect as many as 50 percent
of patients more than 50 years of age.21
FIGURE 8. Dermatomal distribution
of rash in herpes zoster.
Other potential complications of herpes zoster include secondary infection,
meningoencephalitis, transverse myelitis, pneumonitis, hepatitis, myocarditis,
pancreatitis, esophagitis, cystitis, granulomatous arteritis, conjunctivitis and Ramsay
Hunt syndrome (herpes zoster involving the facial and auditory nerves). When herpes
zoster affects the eye (herpes zoster ophthalmicus), an ophthalmologist should always be
consulted.1,20,21

Other Causes
Staphylococcal bacteremia may present with a widespread pustular eruption.
Gonococcemia may also produce a pustular rash, although other lesion types, such as
macules, petechiae and papules, are usually present.3

In immunocompromised patients, disseminated herpes simplex virus infection must be

considered. Patients with underlying liver disease, renal dysfunction or diabetes are
particularly susceptible to infection with Vibrio vulnificus, which is acquired from eating
seafood, exposure to sea water or injury when handling crabs. Rickettsia akari,
transmitted by a house mite, is the cause of rickettsialpox, a mild disease characterized by
a local eschar, a papulovesicular rash and a
mild clinical course.1-4,12

Nodular Eruptions

Erythema Nodosum
Erythema nodosum is an acute inflammatory
and immunologic process involving the
panniculus adiposus (the fatty tissue layer
underlying the skin).1 A number of etiologies
have been identified (Table 4).1,4 This FIGURE 8. Erythema nodosum.
condition is more common in women than in
men.

Presenting features often include fever, malaise and arthralgias. The characteristic
nodules are painful and tender. The lesions most often develop on the lower legs, knees
and arms (Figure 9). The course of erythema nodosum depends on the specific cause, but
spontaneous resolution can be expected within six weeks.1,2

Other Causes
In immunocompromised patients, disseminated fungal infections may produce nodular
lesions. Disseminated candidiasis may present with diffuse nonerythematous nodules in
an immunocompromised patient who has fever and myalgias. Other fungal infections to
consider include cryptococcosis, blastomycosis, histoplasmosis, coccidioidomycosis and
sporotrichosis.2

Rarely, bacteria such as Nocardia, Pseudomonas and Mycobacterium species may

produce nodular lesions.1,4
Common Childhood Rashes
Images of the various rashes may be available by clicking links. In some cases links are
to factual information needed for recognition/management of a systemic disease with
dermatological manifestations. The online dermatological atlas in the internet section will
be useful to find any additional images.

Has the rash got fluid-filled (vesiculobullous) lesions?

Clear fluid

Consider:

• Chickenpox (varicella) - vesicles (initially papules, often not noticed), appearing

as 'drops of water'. Superficial, thin-walled with surrounding erythema rapidly
changing to pustules and crusts. Appears in crops with all stages represented. First
appears on the face and scalp and then spreads to the trunk and extremities. Crusts
fall off in 1-3 weeks leaving a pink base. Initial fever is classically high before
becoming low-grade. Beware of dyspnoea/cough which may indicate varicella-
zoster virus (VZV) pneumonitis.1
• Herpes simplex viral (HSV) infection - eczema herpeticum (HSV infection
superimposed on pre-existing, often mild, eczema causing an eruption of crusty
vesicles and eczematous patches).2
• Impetigo - this usually takes the form of itchy lesions with macules, vesicles,
bullae, pustules and gold-coloured crusts caused by Staphylococcus aureus or
group A beta-haemolytic streptococci.2 Staphylococcal scalded skin syndrome
(appears as scalded skin, due to focal staphylococcal infection – e.g. phage type
71 – releasing an exotoxin).3
• Erythema multiforme, classically appearing as target lesions (erythematous ring
with central bulla)2
• Stevens-Johnson syndrome4
• Toxic epidermal necrolysis4
• Pompholyx (on the hands/feet)5

Pustular rashes

Consider:

• Acne vulgaris (there should be accompanying comedones)6

• Folliculitis (small pustules at the base of hairs)7
• Pustular psoriasis2

Is the rash papular (raised)?2,7

Consider:
 • Urticaria8
• Molluscum contagiosum (pearly or fleshy, umbilicated, i.e. central depression in
papule)
• Scabies (itchy, excoriated, S-shaped burrows, which should be visible with a
magnifying glass)
• Insect bites
• Keratosis pilaris (keratin accumulation at the base of hair follicles)9

Is it red and scaly?

With epidermal breakage (eczematous)?

Atopic eczema, typically involves itching erythematous patches, papules and plaques
with moist crusted erosions on the face, neck and upper trunk, and also the elbows and
knees.

Without epidermal breakage2

Consider:

• Seborrhoeic dermatitis
• Psoriasis
• Tinea corporis/capitis
• Pityriasis rosea

Is it red but not scaly (and NOT purpuric)?

Consider:

• Cellulitis10
• Kawasaki's disease11
• Scarlet fever and the viral exanthemas, for example:
o Roseola infantum – (sixth disease).12
o Primary human herpes virus (HHV-6 and HHV-7). The most common age
is under two years. It is a frequent cause of infantile febrile seizures. Small
blanchable pink macules and papules found on the trunk and neck. It is
associated with high fever prior to defervescence and appearance of a rash
on the fourth day. It is often asymptomatic.13
o Erythema infectiosum - (slapped cheek syndrome or fifth disease) caused
by parvovirus B19.14,15
o Measles - presents as erythematous macules and papules - initially
discrete, may become confluent on the face, neck and shoulders.16 On
mucous membranes, Koplik's spots (tiny bluish-white papules with
erythematous areolae) may develop. Also, upper respiratory tract infection
with cough, malaise and fever subsiding as the rash increases (measles
prodrome = the 4 Cs - cough, coryza, conjunctivitis and very cranky!).
 o Rubella (German measles) pink macules and papules starting on the
forehead and spreading to the face, trunk and extremities on the first day.
Fades from the face on the second day and the rest of the body by the third
day. Petechiae on the soft palate before the rash. Low fever.
o Scarlet fever (= scarlatina) exotoxin-mediated rash (Group A
streptococcus) - sore throat, then general erythema (classically with
perioral sparing), followed by confluent petechiae in skin folds (Pastia's
sign) due to increased capillary fragility. Strawberry tongue (initially
white, then red). Skin desquamation (peeling) frequently follows the
rash.17

Is it red and purpuric?

Consider:

• Meningococcal meningitis (not common but it should be excluded) Early, in 75%

of cases, there is a 2-10 mm macular or maculopapular rash that blanches on
pressure, becoming apparent within the first 24 hours of disease; it is sparsely
distributed on the face, trunk and lower extremities.18 Use the 'glass test' to assess
'blanchability' of the rash by placing a glass tumbler against lesions and applying
pressure. Later the petechiae in the centre of macules become haemorrhagic.
• Henoch-Schönlein purpura19,20
• Idiopathic thrombocytopenic purpura (ITP), leukaemia and other haematological
disorders21
• Trauma, nonaccidental injury
• Enteroviral infections22

Other miscellaneous conditions

• Warts2
• Verrucas
• Head lice7

Algorithm

Summary of Paediatric Skin Rashes: adapted by Dr Adrian M Bonsall, BA (Hons),

MBBS (London) (Hons), MRCPCh (I), FACEM (Primary) from the Paediatric
Handbook 6th Ed. Royal Children's Hospital, Melbourne.
Footnotes23,24

The full list of the original exanthems is:

• First disease = measles or rubeola

• Second disease = scarlet fever
• Third disease = rubella or German measles
• Fourth disease = Filatov's or Dukes' disease
• Fifth disease = erythema infectiosum (slapped cheek syndrome)
• Sixth disease = exanthem subitum or roseola infantum

This ordinal nomenclature came about because, at the turn of the century, there were
classically three exanthematous diseases recognised: measles, rubella and scarlet fever.
Then, in 1900, Dr. Clement Dukes, medical officer at Rugby School, described another
exanthem which he called 'fourth disease'. In 1905 erythema infectiosum (a term already
in use for 6 years applying to the disease described previously by Tshamer and later by
Escherich) was the fifth disease added to the list. Later, sixth disease (roseola infantum)
was recognised and fourth disease was rejected by most observers because of insufficient
evidence to support its existence as an independent entity. So first, second, third and sixth
diseases are now referred to by their more common names, leaving fifth disease as a
solitary reminder of the days when, unaided by sophisticated microbiology, observant
clinician-epidemiologists were able to categorise a group of confusing exanthems.