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Fever and rash in the immunocompetent patient

Official reprint from UpToDate


www.uptodate.com 2014 UpToDate
Fever and rash in the immunocompetent patient
Authors
Fred A Lopez, MD
Charles V Sanders, MD

Section Editor
Peter F Weller, MD, FACP

Deputy Editor
Anna R Thorner, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: May 2014. | This topic last updated: Jan 23, 2014.
INTRODUCTION Fever with an accompanying rash is a common symptom constellation in patients presenting to clinicians' offices and
emergency departments. Skin manifestations may provide the only early clue to an underlying infection, may be the hallmark of contagious
disease, and/or may be an early sign of a life-threatening infection. The differential diagnosis of fever and rash is extremely broad, but this
symptom complex provides an opportunity for the diligent clinician to establish a probable etiology through a careful history and physical
examination.
A systematic approach is crucial for establishing a timely diagnosis, determining early therapy when appropriate, and considering isolation of
the patient if necessary. Epidemiologic clues are important to pursue such as [1-6]:
Age of the patient
Season of the year
Travel history
Geographic location
Exposures including to insects, animals, and ill contacts
Medications
Immunizations and history of childhood illnesses
The immune status of the host
Features of the rash are also important to consider, including:
Characteristics of the lesions
Distribution and progression of the rash
Timing of the onset in relation to fever
Change in morphology, such as papules to vesicles or petechiae
Despite the strong association between the syndrome of fever and rash and infectious diseases, a variety of noninfectious processes can
also cause similar presentations, including deep venous thrombosis, superficial thrombophlebitis, erythromelalgia, relapsing polychondritis,
foreign body reactions, drug reactions, gouty arthritis, cutaneous lupus erythematosus, and erythema nodosum [7]. The approach to the
immunocompetent patient with fever and rash and selected presentations that constitute emergencies will be reviewed here. Specific
infections with characteristic rashes and fever and rash in immunocompromised patients are discussed separately. (See "Infectious causes
of fever and rash in non-HIV immunocompromised hosts" and "Fever and rash in HIV-infected patients".)
EPIDEMIOLOGY AND ETIOLOGY Epidemiologic features are extremely helpful in the approach to a patient with a fever and rash [1-4].
Diseases that present in childhood The age of the patient often assists in narrowing the differential diagnosis. Exanthems associated
with a variety of viral illnesses are classically seen in the pediatric age group [8]. The constellation of symptoms and a characteristic rash
often allow for a clinically based diagnosis, as illustrated by the following disorders.
Measles (rubeola) is associated with a blanching erythematous "brick-red" maculopapular rash beginning in the head and neck area and
spreading centrifugally to the trunk and extremities; patients also complain of fever, cough, coryza, and conjunctivitis (picture 1). (See
"Clinical presentation and diagnosis of measles".)
Chickenpox is characterized by classic vesicular lesions on an erythematous base that appear in crops and are present in different
stages from papules through vesicles to crusting (picture 2). (See "Clinical features of varicella-zoster virus infection: Chickenpox".)
Rubella has a rash that resembles measles, but the patient does not appear to be sick; prominent postauricular, posterior cervical,
and/or suboccipital adenopathy also assists in the diagnosis. Forscheimer spots, or punctate soft palate macules, can represent a
helpful clue.
Erythema infectiosum (fifth disease) is due to human parvovirus B19. Children, unlike adults, often develop a characteristic rash with a
"slapped cheeks" appearance (picture 3). (See "Clinical manifestations and pathogenesis of human parvovirus B19 infection".)
Roseola infantum or exanthem subitum, a human herpesvirus 6 or 7 infection primarily seen in infants, is characterized by high fever for
three to four days, followed by seizures and a generalized maculopapular rash that spreads from the trunk to the extremities but spares
the face. (See "Roseola infantum (exanthem subitum)" and "Human herpesvirus 7 infection", section on 'Primary infection'.)
Other infections accompanied by rash also occur primarily in children:
Scarlet fever is an exotoxin (erythrogenic toxin)-mediated diffuse erythematous rash occurring most commonly in the setting of
pharyngitis from group A Streptococcus (GAS) infection. Scarlet fever is manifested by a coarse, sandpaper-like, erythematous,
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Fever and rash in the immunocompetent patient

blanching rash, which ultimately desquamates. This is accompanied by circumoral pallor and a strawberry tongue. (See "Complications
of streptococcal tonsillopharyngitis".)
Acute rheumatic fever (ARF) is another potential sequela of group A streptococcal pharyngeal infection. The classic dermatologic
manifestations of ARF are erythema marginatum (transient macular lesions with central clearing found on the extensor surfaces of the
proximal extremities and trunk) and subcutaneous nodules often located over bony prominences. (See "Complications of streptococcal
tonsillopharyngitis" and "Clinical manifestations and diagnosis of acute rheumatic fever".)
Kawasaki syndrome, a disease of unknown etiology, is usually seen in children less than four years of age. In addition to fever lasting
>5 days, some of the criteria for this syndrome, as defined by the Centers for Disease Control and Prevention (CDC), are bilateral
conjunctival injection, injected or fissured lips, injected pharynx or 'strawberry tongue' (picture 4), erythema of the palms or soles,
edema of the hands or feet, or generalized or periungual desquamation, rash, and cervical lymphadenopathy [9]. (See "Kawasaki
disease: Clinical features and diagnosis".)
Nonpolio enteroviruses (coxsackievirus, echovirus) can cause a variety of rashes and should always be included in the differential
diagnosis of a young child with fever and rash of undetermined etiology. (See "Clinical manifestations and diagnosis of enterovirus and
parechovirus infections".)
An evaluation for Epstein-Barr virus (EBV)associated infectious mononucleosis should be undertaken in older children and adolescents
who present with fever, malaise, sweats, anorexia, nausea, chills, sore throat, posterior cervical lymphadenopathy, splenomegaly, and a
maculopapular rash, especially after the administration of ampicillin (picture 5). The rash is usually over the trunk but can involve the
extremities, including the hands and feet. Other causes of infectious mononucleosis are discussed below. (See 'Selected diseases that
present in adulthood' below and "Infectious mononucleosis in adults and adolescents".)
Adolescents and young adults with pharyngitis, fever, lymphadenopathy, and/or maculopapular/scarlatiniform rash whose work-up is
negative for group A Streptococcus and viral-associated mononucleosis may be infected with Arcanobacterium haemolyticum, a grampositive rod that appears to be more susceptible to erythromycin than to penicillin [10]. This infection is seen primarily in patients who
are 15 to 18 years of age, and the rash, which can be pruritic, is typically seen first over the extensor surfaces before spreading
centrally [10]. The rash usually spares the face.
Mycoplasma infection may be accompanied by skin findings, which include a mild erythematous maculopapular or vesicular rash,
erythema multiforme, or the Stevens-Johnson syndrome. (See "Mycoplasma pneumoniae infection in children", section on 'Skin
disease'.)
Selected diseases that present in adulthood Exanthems associated with a variety of viral illnesses can be seen in adults. Several to
consider include:
Measles (rubeola) is associated with a blanching erythematous "brick-red" maculopapular rash beginning in the head and neck area and
spreading centrifugally to the trunk and extremities (picture 1); patients also complain of fever, cough, coryza, and conjunctivitis.
Despite the availability of an effective measles vaccine, measles outbreaks continue to occur [11]. (See "Clinical presentation and
diagnosis of measles" and "Epidemiology and transmission of measles".)
Infectious mononucleosis can be caused by several different pathogens. Young adults who present with fever, malaise, sweats,
anorexia, nausea, chills, sore throat, posterior cervical lymphadenopathy, splenomegaly, and a maculopapular rash, especially after the
administration of ampicillin, should undergo an evaluation for Epstein-Barr virus (EBV)associated infectious mononucleosis (picture 5).
The rash is usually over the trunk but can involve the extremities, including the hands and feet. About half of all college freshmen have
EBV-associated antibodies, and up to 20 percent of those who do not are expected to seroconvert annually during these years.
Importantly, these cases are usually asymptomatic [12]. (See "Infectious mononucleosis in adults and adolescents".)
Cytomegalovirus should be considered in the heterophile antibody-negative patient with infectious mononucleosis, although
lymphadenopathy and pharyngitis may not be as prominent.
The acute retroviral syndrome that may occur approximately two to four weeks after primary HIV infection is a mononucleosis-like
illness characterized by fever, sore throat, malaise, headache, lymphadenopathy, mucocutaneous ulceration, and rash. The rash, seen
in more than 50 percent of patients, is usually transient, maculopapular, nonpruritic, and truncal or facial in location. (See "Acute and
early HIV infection: Pathogenesis and epidemiology".)
Adolescents and young adults with pharyngitis, fever, lymphadenopathy, and/or a maculopapular/scarlatiniform rash whose evaluation is
negative for group A Streptococcus and viral causes of mononucleosis may be infected with Arcanobacterium haemolyticum, a grampositive rod that appears to be more susceptible to erythromycin than to penicillin [10]. This infection is seen primarily in patients who
are 15 to 18 years of age and the rash, which can be pruritic, is typically seen first over the extensor surfaces before spreading centrally
[10]. The rash usually spares the face.
Approximately 20 percent of cases of erythema infectiosum occur in adults [13]. Constitutional symptoms in primary infection are more
pronounced in adults and typically include lymphadenopathy, arthritis, and fever. The rash, when present, is often described as first
macular and then lacy and reticulated, spreading initially from the limbs to the trunk and buttocks. (See "Clinical manifestations and
pathogenesis of human parvovirus B19 infection".)
Individuals who did not have chickenpox during childhood may develop it later in life. Those who did have chickenpox may develop
herpes zoster (shingles), which is caused by reactivation of latent varicella zoster virus. Incidence and severity increases with age and
with increasing immunosuppression. In immunocompetent individuals, herpes zoster is typically manifested as vesicular lesions
distributed along a dermatome and ending at the midline (picture 6). (See "Clinical features of varicella-zoster virus infection:
Chickenpox" and "Clinical manifestations of varicella-zoster virus infection: Herpes zoster".)
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Mycoplasma infection may be accompanied by skin findings, which range from a mild erythematous maculopapular or vesicular rash to
the Stevens-Johnson syndrome. (See "Mycoplasma pneumoniae infection in adults", section on 'Skin disease'.)
Season of the year A number of infections characterized by fever and rash have a distinct seasonal predisposition. As examples,
nonpolio enteroviral infections occur in the summer and fall months; Kawasaki syndrome, meningococcal infection, and parvoviral infections
present most commonly in the winter or early spring months; measles and rubella are more frequent in the spring; tick-borne diseases such
as Lyme disease, ehrlichiosis, and Rocky Mountain spotted fever (RMSF) primarily occur in the spring and summer; tularemia and plague are
usually seen in the summer. Vibrio vulnificus infections occur between the months of April and October, when warmer waters facilitate
propagation of this organism. Septicemia due to this organism typically occurs after consumption of raw seafood (usually oysters). Vibrio
vulnificus and V. parahaemolyticusassociated wound infections can occur after injury to skin in contaminated water (eg, after natural
disasters) [14,15]. (See "Vibrio vulnificus infections".)
Geography Travel to or residence in specific areas of the continental United States or other parts of the world can provide important clues
for the diagnosis of fever and rash [16-18]. Examples associated with a principal location in the United States include:
Rocky Mountain spotted fever South-central and Atlantic states
Human monocytic ehrlichiosis Midwestern, south-central, and southeastern states
Lyme disease The Pacific northwest, the midwest, and the northeast
The tick vectors for tularemia Western, southeastern, and south-central states
Plague Western states
Relapsing fever due to Borrelia hermsii Mountainous areas of the western United States
Endemic fungal infections including Blastomyces dermatitidis (southeastern states), Coccidioides immitis (southwestern states), and
Histoplasma capsulatum (Mississippi and Ohio River valleys)
Several informative reviews on skin manifestations of infections in areas of the world other than the United States are available [19,20]. The
CDC website (www.cdc.gov/travel/index.htm) is an excellent resource for prospective travelers to other areas of the world. (See "Travel
advice".) A number of entities, characterized by rash but not always fever, merit consideration in individuals residing in or returning from trips
to international sites [21,22].
Cutaneous leishmaniasis, which can present with papular, nodular, or ulcerative lesions, occurs in an Old World and New World form
caused by different species. Leishmania tropica, L. major, or L. aethiopica occurs in patients who live in or who have visited the Middle
East, Far East, or Africa (Old World cutaneous leishmaniasis) (picture 7). New World cutaneous leishmaniasis is caused by different
species in Central and South America. L. braziliensis in South America causes ulcerative lesions with the subsequent development of
disfiguring oral, pharyngeal, or nasal lesions. Leishmaniasis has also been reported in central and southern Texas in patients who have
not traveled to areas endemic for this organism [23].
Trypanosoma cruzi, which causes Chagas disease, is found in South and Central America. Findings can include Romaa's sign, a
combination of unilateral conjunctivitis and eyelid edema (picture 8) or the chagoma, an indurated nodular lesion.
Skin manifestations of schistosomiasis, acquired by wading or swimming in fresh water, can include nonspecific maculopapular lesions
or characteristic verrucoid lesions known as Bilharzia cutaneous tarda. The most common species infecting humans include
Schistosoma haematobium (Africa, Middle East), S. mansoni (Africa, Middle East, South America), and S. japonicum (eastern Asia). In
addition, in North America similar maculopapular lesions ("swimmer's itch") may develop after swimming or wading in water that
contains cercariae of avian and other non-human schistosome species. (See "Epidemiology, pathogenesis, and clinical features of
schistosomiasis", section on 'Swimmer's itch'.)
Dengue virus infections are increasing in incidence, and its primary vector, the Aedes aegypti mosquito, inhabits nearly all tropical
latitudes, including the United States [24]. Skin manifestations can include a transient macular rash early in the infection and a
generalized morbilliform-like rash sparing the palms and soles when fever resolves on approximately day five. Petechiae, purpura, and
ecchymoses are more likely to be seen in dengue hemorrhagic fever or dengue shock syndrome, severe presentations of dengue virus
seen in previously sensitized patients [25]. (See "Clinical manifestations and diagnosis of dengue virus infections".)
Chikungunya fever caused by the mosquito-transmitted chikungunya virus is characterized by fever, rash, painful polyarthralgias,
headache, fatigue, myalgias, and gastrointestinal symptoms. The rash is typically described as macular, maculopapular, vesicular,
bullous, or petechial [26,27]. Outbreaks have been reported in sub-Saharan Africa, southeast Asia and India, islands in the Indian
Ocean, Italy, and the Caribbean. The average incubation period is three to seven days. (See "Chikungunya fever".)
A variety of parasitic larvae can cause a "creeping eruption" known as cutaneous larva migrans. (See "Cutaneous larva migrans
(creeping eruption)".) Typically, dog and cat hookworm larvae enter the skin of the foot and cause a migratory, pruritic erythematous
serpiginous lesion observed intermittently until the parasite's death in the human, a dead-end host (picture 9). These infections are
found worldwide in tropical and subtropical areas and commonly originate on sandy shores.
The southern United States, Asia, Africa, Central America, and parts of eastern Europe are geographic foci for infection with the
nematode Strongyloides stercoralis. (See "Strongyloidiasis".) Skin lesions are polyphasic early but may become maculopapular or
urticarial in chronic infection. The classic and pathognomonic lesion of this helminthic infection is larva currens, a short-lived but
recurrent pruritic, migratory, serpiginous rash involving the thighs or perineum.
Travelers returning from Africa, Central America, and South America who develop painless subcutaneous nodules (usually on the head
or bony prominences) or a pruritic dermatitis may have onchocerciasis, a nematode (Onchocerca volvulus) infection transmitted by the
black fly (picture 10). (See "Onchocerciasis".)
Travelers returning from the northeastern or southern African bush country, India, the Mediterranean, or Russia who present with a small
(less than 1 cm) necrotic ulcer with surrounding erythema ("tache-noire") and subsequently develop fever, headache, regional
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lymphadenopathy, and a diffuse maculopapular skin rash may have Boutonneuse fever secondary to tick-associated Rick ettsia conorii
infection. Similar presentations may be seen in travelers returning from eastern Australia who are infected with R. australis
("Queensland fever"), from northern Asia who are infected with R. sibirica ("North Asian fever"), or from Japan who are infected with R.
japonica ("Oriental spotted fever"). Included in this group of "spotted fevers" is the mouse mite associated rickettsialpox caused by R.
ak ari; it is seen in urban areas of the United States, Russia, and South Africa (see "Potential health hazards in travelers to Australia,
New Zealand, and the southwestern Pacific (Oceania)" and "Rickettsialpox"). Scrub typhus, a potentially fatal rickettsial infection
transmitted by mites, is characterized by a maculopapular rash, and in some patients, eschars. This entity can be seen in travelers to
southeast Asia, the southern and western Pacific, Nepal, India, Korea, Australia, and China. (See "Scrub typhus: Clinical features and
diagnosis".)
Typhoid fever can occur in travelers to endemic areas like Mexico or India who ingest food or water contaminated by fecal matter. The
skin manifestations are small, blanching papules called rose spots, usually found on the trunk, which typically arise in the second week
of infection and fade within several days. (See "Epidemiology, microbiology, clinical manifestations, and diagnosis of typhoid fever".)
Incubation period Knowledge of the incubation period for infectious agents is particularly helpful to the physician trying to determine the
significance of a rash in a patient exposed to another individual with a similar exanthem. A range of incubation periods exists for selected
infectious agents that may be associated with fever and rash (table 1A-B).
Exposure history The category of exposures is a broad one in the differential diagnosis of fever and rash. Exposures to food, water, plant
materials, animals, and infected human secretions can lead to rashes and can be associated with both occupational and nonoccupational
contacts. As an example, the herpetic whitlow, seen in dental workers exposed to HSV-infected mucous membranes and secretions, is a
classic occupation-associated infection (picture 11). Animal handlers, pet owners, and laboratory workers are more vulnerable to such
infections, including [28-30]:
Toxoplasmosis and cat scratch disease from cats and kittens (picture 12) (see "Microbiology, epidemiology, clinical manifestations,
and diagnosis of cat scratch disease")
Psittacosis from poultry, finches, or parrots (see "Psittacosis")
Cryptococcosis from pigeon, dog, or cat feces
Plague from goats, rabbits, dogs, squirrels, or coyotes (see "Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis
infection)")
Rat bite fever or leptospirosis from rats
Tularemia in sheep handlers, wild game cooks, pelt dealers, and veterinarians, which can result in ulceroglandular, oculoglandular,
glandular, oropharyngeal, typhoidal, or pneumonic syndromes [31] (picture 13)
Pasteurella-associated wound infections secondary to cat and dog bites [32]
Other environmental occupational exposures include:
Papular or nodular lymphocutaneous lesions that develop on the extremities after trauma associated with an aquarium or swimming
pool or after handling seafood are consistent with Mycobacterium marinum infections ("fish tank granuloma") [33,34].
Percutaneous injuries inflicted while handling the fish tilapia have been reported to cause Streptococcus iniae cellulitis of the hand [35].
Erysipelothrix rhusiopathiae, a gram-positive rod whose major host is swine, can produce a localized violaceous, cellulitic process
involving primarily the hands or fingers in fish and meat handlers (picture 14).
A gram-negative rod known as Edwardsiella tarda can cause fresh waterassociated wound infections. Skin and soft tissue infections
caused by this organism include abscesses, necrotizing fasciitis, bullae, myonecrosis, necrotizing fasciitis, and cellulitis [36].
Individuals who work with plants and soil (ie, florists, gardeners, farmers) are at risk for developing sporotrichosis, an infection of the
extremities caused by the dimorphic fungus Sporothrix schenck ii (picture 15). (See "Clinical features and diagnosis of sporotrichosis".)
A variety of conditions accompanied by fever and rash result from arthropod exposures. As examples, black flies are associated with
onchocerciasis, deer flies with loiasis, fleas with plague and endemic typhus, mosquitoes with malaria, dengue fever, and chikungunya fever,
assassin or reduviid bugs with Chagas disease, and sand flies with leishmaniasis.
A report from the western United States described 15 patients with West Nile Virus fever who presented with a generalized maculopapular
rash. A tingling and burning sensation was reported by four patients (27 percent) and pruritus by five patients (33 percent) [37].
The spirochete Borrelia burgdorferi is the etiologic agent of Lyme disease, an ixodid tick-associated infection seen in the United States. The
classic skin lesion in this infection is erythema migrans (EM), a red expanding plaque-like lesion with central clearing that develops at the
site of the tick bite (picture 16). (See "Clinical manifestations of Lyme disease in adults".)
Other tick-borne diseases seen in the United States include:
Ehrlichiosis can present as human monocytic ehrlichiosis (HME) caused by Ehrlichia chaffeensis or human granulocytic anaplasmosis
(HGA) due to Anaplasma phagocytophilum [38]. Rash may or may not accompany ehrlichia infection which has also been termed
"Spotless Rocky Mountain spotted fever" [39]. A rash is much more likely to be seen in cases of HME than HGE [40]. (See "Human
ehrlichiosis and anaplasmosis".)
Rick ettsia rick ettsii, the etiologic agent of RMSF, can be transmitted by the dog or wood tick and is primarily seen in the south-central
and south Atlantic United States (see below). (See "Clinical manifestations and diagnosis of Rocky Mountain spotted fever".)
Southern tick-associated rash illness (STARI), presumably caused by a spirochete carried by Amblyomma americanum ticks, is
characterized by a flu-like illness and an erythema migranslike rash. STARI should be considered in areas where A. americanum ticks
are present, but where Lyme disease is absent or uncommon [41]. (See "Southern tick-associated rash illness (STARI)".)
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Recreational activities can result in infections associated with characteristic skin lesions. Exposure to hot tubs or whirlpools can cause
Pseudomonas aeruginosa folliculitis (picture 17) [42]; whirlpool footbaths have also been associated with Mycobacterium fortuitum
associated furuncles in individuals who had pedicures [43]. Swimming in contaminated lake water has been associated with the development
of hemolytic-uremic syndrome with thrombocytopenia-associated petechial skin lesions [44]. Herpes gladiatorum skin infections have been
described in athletes who engage in contact sports like rugby and wrestling [45,46], and outbreaks of group A streptococcal and
staphylococcal skin infections can occur in American and European football players after competition [47-49]. In one report, a cutaneous
larva migrans infection secondary to Ancylostoma braziliense was observed in a beach volleyball player [50].
Medication history Although drugs can cause a plethora of skin lesions, the relationship between drug fever and rash may not be as
strong as many physicians believe. In one systematic analysis of 148 episodes of drug fever, fewer than 20 percent were associated with
rash, and fewer than 50 percent of the rashes were urticarial in nature [51]. Hypersensitivity or allergic-type skin reactions (rash, itching, or
hives) were evaluated in over 20,000 hospitalized patients in the Boston Collaborative Drug surveillance program, and though associated fever
was not evaluated, only about 2 percent of patients receiving drugs developed cutaneous reactions [52]. Antibiotics such as penicillins,
cephalosporins, and trimethoprim-sulfamethoxazole were associated with high rates of allergic skin reactions. Other drugs classically
associated with fever and hypersensitivity reactions include barbiturates, phenytoin, procainamide, and quinidine. However, only one in every
1000 hospitalized patients develops a severe cutaneous drug reaction like Stevens-Johnson syndrome or toxic epidermal necrolysis [53]. A
metabolic predisposition leading to ineffective detoxification of sulfonamide and anticonvulsant metabolites may lead to severe adverse
cutaneous drug reactions [54]. These reactions typically develop one to three weeks after the initiation of the culprit agent [55]. (See
"Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)
Immunization history Inadequately immunized individuals are susceptible to the traditional childhood viral infections and serve as an
often overlooked reservoir of disease. The current recommended immunizations for children in the United States include hepatitis A and B,
diphtheria and tetanus toxoids and pertussis, Haemophilus influenzae type b, rotavirus, poliovirus, measles-mumps-rubella (MMR), varicella,
influenza, human papillomavirus, pneumococcus, and meningococcus (in adolescents).
Follow-up of older children with their primary care physicians provides an opportune time for confirming appropriate immunizations. (See
"Standard immunizations for children and adolescents".)
Similarly, zoster vaccination is recommended for adults 60 years of age and older to decrease the incidence of zoster and postherpetic
neuralgia. (See "Prevention of varicella-zoster virus infection: Herpes zoster", section on 'The use of zoster vaccine'.)
Sexual history A thorough sexual history is essential in evaluating the patient with a rash of unknown etiology. Genital or rectal
ulcerations may be caused by a variety of infectious agents, including syphilis (picture 18), herpes simplex (picture 19), lymphogranuloma
venereum (picture 20), chancroid (picture 21), and donovanosis (picture 22 and table 2A-B). These infections may not be associated with
fever.
Syphilis can have a variety of cutaneous manifestations. The primary stage is characterized by the chancre, a painless, often solitary,
indurated genital ulceration with elevated, well-defined borders. The skin lesions of secondary syphilis include a generalized papular or
maculopapular rash (rarely pustular) that also affects the palms and soles (picture 23). Other lesions seen during this stage include
condylomata lata, flat moist condylomata-like lesions that are gray, infectious, and located around the genitals, mouth, anus, and other moist
areas (picture 24). Approximately 15 to 30 percent of infected patients will manifest mucous membrane ulcerations that are sharply
demarcated and covered with a gray exudate, (ie, mucous patches). Patchy alopecia resulting in a "moth-eaten" appearance of the scalp can
also be seen during this stage. (See "Pathophysiology, transmission, and natural history of syphilis".)
Classic skin lesions of late, or tertiary, syphilis include the gumma, generally a solitary granulomatous subcutaneous skin or mucous
membrane lesion that is initially nodular before ulcerating. Enlargement of these lesions can result in local tissue destruction. Also seen in
tertiary syphilis are noduloulcerative lesions arranged in characteristic ring-like patterns known as lues maligna (picture 25). Resolution of
these lesions results in hyperpigmented scars.
Disseminated gonococcal infection causes a rash in as many as 90 percent of patients. The rash consists of fewer than 20 to 30 papular,
nodular, and/or petechial lesions that develop a vesiculopustular component and then, finally, a necrotic, hemorrhagic appearance [56]. The
rash contains lesions that, like those of primary varicella infection, are in different stages of evolution. (See "Disseminated gonococcal
infection".)
The acute retroviral syndrome that occurs approximately two to six weeks after primary human immunodeficiency syndrome (HIV) infection is
characterized by fever, sore throat, malaise, headache, lymphadenopathy, mucocutaneous ulceration, and rash. The rash, seen in more than
50 percent of patients, is usually transient, maculopapular, nonpruritic, and truncal or facial in location [57]. This presentation can often be
confused for infectious mononucleosis [58]. (See "Acute and early HIV infection: Pathogenesis and epidemiology".)
Immunocompetence of the host The possible etiologies of fever and rash are quite different if the host is immunosuppressed. Thus,
determining the underlying immunologic status of the host is essential in assessing any patient with fever and rash [59].
DIAGNOSTIC APPROACH The diagnostic approach to the patient with fever and rash should focus on the appearance of the rash in
addition to the detailed epidemiologic history listed above.
Characteristics of the rash A history of the rash should include the following questions [5]:
Was a prodrome present?
Where and when did the rash start?
How has the rash progressed anatomically?
Has the rash changed in appearance?
Has any treatment been instituted for the rash?
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In examining a rash, it is essential to characterize the lesions, both individually and collectively, according to morphology and arrangement
(annular, linear, serpiginous, dermatomal, etc), distribution (isolated versus generalized, bilateral versus unilateral, symmetric, occurring on
exposed areas, etc), and evolution (centrifugal versus centripetal) [5,60]. In addition, a differential diagnosis for fever and rash can be based
upon the appearance of the rash and its accompanying signs (table 3A-C and table 4A-B). The following definitions are useful in interpreting
the tables and characterizing lesions and rashes [61]:
Macule Nonpalpable, circumscribed lesion that is flat and less than 1 cm in diameter
Papule Palpable lesion that is solid, elevated, and less than 1 cm in diameter
Maculopapular Confluent, erythematous rash made up of both macular and papular lesions
Purpura Papular or macular nonblanching lesions that are due to extravasation of red blood cells
Nodule Deep-seated, roundish lesion less than 1.5 cm in diameter that can involve the epidermal, dermal, and/or subcutaneous tissue
Plaque A palpable elevated lesion greater than 1 cm in diameter
Vesicle A distinct, elevated skin lesion that contains fluid and is less than 1 cm in diameter
Bulla A vesicle that is more than 1 cm in diameter
Pustule A vesicle that contains pus
Ulcer Loss of the epidermis and upper layer of the dermis, resulting in a depressed skin lesion
While these categories are useful and descriptive, many rashes have overlapping features, and a number of infectious agents can present
with several different rash morphologies. Different infectious agents can also produce similar types of rashes.
Several skin conditions can be identified based upon appearance but can be caused by a variety of infectious and noninfectious etiologies.
Erythema multiforme Symmetrically distributed "target" lesions that typically involve the palms, soles, and mucous membranes,
reflecting epidermal and dermal involvement (picture 26 and table 5) (see "Pathogenesis, clinical features, and diagnosis of erythema
multiforme")
Erythema nodosum Painful red nodular lesions usually found symmetrically on the lower extremities and representing inflammation in
the panniculus (picture 27) (see "Erythema nodosum")
Toxic epidermal necrolysis A severe skin and mucosal disorder that manifests initially as tender widespread erythema with
subsequent loss of the epidermis, usually due to drugs such as sulfonamides, allopurinol, nonsteroidal antiinflammatory drugs, and
anticonvulsants (picture 28 and table 6)
Urticaria A skin condition associated with the presence of transient wheals (ie, papules or plaques) due to dermal edema, with no
evidence of epidermal involvement or abnormality (picture 29 and table 7) (see "New onset urticaria")
Enanthems are mucous membrane lesions often associated with exanthems in systemic infectious diseases. Examples include oral or
genital mucous patches (secondary syphilis), oral gummatous lesions (tertiary syphilis), oral ulcers (disseminated histoplasmosis,
gonococcus, or tuberculosis), palatal petechial lesions (rubella and EBV mononucleosis), oral vesicular lesions (Coxsackie-associated hand,
foot, and mouth syndrome, varicella, and primary HSV), and strawberry tongue (scarlet fever, Kawasaki syndrome, toxic shock syndrome).
Koplik's spots, the tiny punctate elevated white buccal mucosa lesions located adjacent to the lower molars, are pathognomonic of measles
and can precede the rash by 24 to 48 hours.
Physical examination A thorough physical examination should focus on the following [5]:
Vital signs
General appearance to assess the severity of illness
Strict attention to lymph nodes, mucous membranes, conjunctivae, and genitalia
Meningeal signs and complete neurologic evaluation
Liver and spleen size
Joint examination
Skin examination (table 3A-C and table 4A-B).
Laboratory testing Appropriate laboratory testing includes [5]:
Nonspecific tests such as complete blood count and urinalysis
Blood cultures, including specific media and isolation methods for work-up of bacteria, mycobacterial, and fungal organisms should be
inoculated prior to beginning antimicrobial therapy
Serologic tests, when appropriate (eg, for Coccidioides immitis, hepatitis B, Toxoplasma gondii, Borrelia burgdorferi, Treponema
pallidum, dengue fever, and HIV)
Antigen tests, when appropriate (eg, serum cryptococcal antigen)
Fluid from vesicular, pustular, petechial, ulcerative, and bullous lesions can be examined. Vesicular lesions should be unroofed so that the
base of the lesion can be swabbed; herpes simplex virus and varicella-zoster virus can be distinguished with rapid fluorescent antibody
studies. Viral culture can also be performed. Aspirated fluid from pustules and bullous lesions should be Gram stained and cultured in an
expeditious fashion by the microbiology laboratory. In suspected cases of syphilis, exudative material from the ulcer base can be examined
by darkfield microscopy. (See "Diagnostic testing for syphilis".)
Skin biopsy can be particularly useful in establishing a diagnosis for nodular lesions but can also be obtained for petechial-purpuric,
maculopapular, and ulcerative rashes. Aseptically obtained biopsy material should be sent to the microbiology and pathology laboratories for
appropriate culture and histopathologic evaluation. In suspected cases of Rocky Mountain spotted fever, direct immunofluorescent
demonstration of rickettsial organisms is diagnostic. (See "Clinical manifestations and diagnosis of Rocky Mountain spotted fever".)
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SELECTED FEVER AND RASH EMERGENCIES Several infections associated with fever and rash constitute emergencies that must be
recognized promptly by the evaluating clinician.
Meningococcal infection The gram-negative diplococcus N. meningitidis can cause life-threatening infection in children and young
adults; outbreaks of infection can occur, especially among groups with confined living conditions, such as military bases, day care centers,
and dormitories. The infection can also develop in individuals with congenital late terminal complement deficiency, acquired complement
deficiency (ie, nephrotic syndrome, systemic lupus erythematosus), and splenectomy. (See "Epidemiology of Neisseria meningitidis
infection".)
Meningococcal infection can result in a number of different clinical presentations, but meningococcemia and/or meningitis are the most
common. In addition to fever, myalgia, somnolence, headache, and nausea, rash occurs in most patients with meningococcemia. Early
lesions may be macular, but rapidly increasing numbers of petechial or purpuric lesions can develop on the distal extremities and trunk,
usually sparing the palms and soles (in contrast to RMSF) (picture 30). An urticarial rash can also be seen [62]. Lesions on mucosal
surfaces are also common. (See "Clinical manifestations of meningococcal infection".)
In one review of 151 patients with meningococcal infection, 75 percent had petechial/maculopapular lesions, 11 percent purpuric/ecchymotic
lesions, and 14 percent no skin lesions [63]. Mortality was considerably higher in those with purpuric/ecchymotic lesions.
Meningococcemia may be rapidly fatal, with mortality rates of approximately 10 to 25 percent. Prompt recognition, supportive therapy to
maintain adequate blood pressure and oxygenation, and pathogen-directed therapy with parenteral antibiotics (usually high doses of penicillin
or a third-generation cephalosporin) are essential. Purpura fulminans, a particularly severe complication of meningococcemia, refers to the
fulminant hemorrhagic skin necrosis that can be seen in association with disseminated intravascular coagulation (DIC) and shock. (See
"Treatment and prevention of meningococcal infection".)
Bacterial endocarditis Skin lesions may offer a clue to the underlying diagnosis of infective endocarditis (IE). Associated peripheral
cutaneous or mucocutaneous lesions include petechiae, splinter hemorrhages, Janeway lesions, Osler's nodes, and Roth spots. (See
"Clinical manifestations and diagnosis of infective endocarditis" and "Infective endocarditis: Historical and Duke criteria".)
Petechiae are not specific for infective endocarditis but are its most common skin manifestation. They may be present on the skin, usually on
the extremities, or on mucous membranes such as the palate or conjunctivae, the latter usually as hemorrhages best seen with eversion of
either upper or lower eyelids (picture 31). Splinter hemorrhages, also nonspecific for endocarditis, are nonblanching, linear reddish-brown
lesions found under the nail bed (picture 32).
Janeway lesions, Osler's nodes, and Roth spots are more specific for IE but also less common; Roth spots are particularly rare. Janeway
lesions are macular, nonblanching, nonpainful, and erythematous lesions on the palms and soles (picture 33). By contrast, Osler's nodes are
painful, violaceous nodules found in the pulp of fingers and toes and are seen more often in subacute than acute cases of IE (picture 34).
Roth spots are exudative, edematous hemorrhagic lesions of the retina. Of note, conjunctival hemorrhage, Janeway lesions, Osler's nodes,
and Roth spots are included as minor criteria in the Duke criteria for the diagnosis of infective endocarditis [64].
It is important to recognize the skin manifestations of endocarditis in order to obtain blood cultures and initiate appropriate therapy. A
prospective cohort study reported that S. aureus is the most common cause of infective endocarditis in many locations worldwide [65].
Despite improvements in therapy and the availability of surgical intervention, there is still an appreciable mortality rate of 25 to 40 percent for
patients with S. aureus IE who are not injection drug users [66]. (See "Clinical manifestations of Staphylococcus aureus infection".)
Significantly, the incidence of infective endocarditis has remained unchanged in the last 20 years [67].
Rocky Mountain spotted fever Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by Rick ettsia rick ettsii. After an
incubation period of as little as two days, fever, headache, malaise, conjunctival suffusion, and myalgia usually develop. In most patients, a
rash appears within the following week, initially on the wrists and ankles and later on the palms and soles, before spreading centripetally to
include the arms, legs, face, and trunk.
The differential diagnosis includes meningococcemia, infective endocarditis, measles, secondary syphilis, and other rickettsial diseases. The
rash is at first erythematous and maculopapular. Progression to a petechial rash is often noted and, in severe cases of RMSF, purpura and
hemorrhagic necrosis can occur (picture 35). Associated thrombocytopenia can make the diagnosis of RMSF difficult to distinguish from
meningococcemia. However, several clinical clues favor the diagnosis of RMSF, including a history of tick bite or visits to areas where RMSFassociated ticks are present, occurrence of the rash a median of three to four days following the onset of fever, relative leukopenia, and
elevated aminotransferases. (See "Clinical manifestations and diagnosis of Rocky Mountain spotted fever".)
Toxic shock syndrome Initially used in the late 1970s to describe a disease syndrome in children infected with S. aureus, toxic shock
syndrome (TSS) became a well-known entity in the early 1980s when its association with young menstruating women and tampon use was
described [68-70]. Nonmenstrual toxic shock syndrome has been associated with surgical wounds, burns, skin ulcerations, catheters, and
nasal packings. (See "Staphylococcal toxic shock syndrome".)
Criteria for the diagnosis of TSS include a temperature above 38.9C, hypotension, a desquamating rash, involvement of at least three organ
systems, and exclusion of clinical mimics such as RMSF, leptospirosis, and measles [71]. Multiple toxins have been described in
association with this syndrome, particularly TSS toxin (TSST-1) in menstrual-associated TSS [72].
The rash seen in TSS is diffuse and erythematous and can resemble a sunburn (picture 36). The conjunctivae are also often involved (picture
37). Fever, diarrhea, muscle aches, and nausea/emesis are commonly present. Desquamation, usually of the palms and soles or at the sites
of the original rash, is classically described one to three weeks later.
Group A streptococci (GAS) can also produce a toxic shocklike syndrome, most often in association with a skin or soft tissue infection.
(See "Epidemiology, clinical manifestations, and diagnosis of streptococcal toxic shock syndrome".)
Streptococcal pyrogenic exotoxins that cause cytokine production, analogous to staphylococcal TSST-1, appear to be responsible for
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initiating this syndrome. Several general differences are noted between TSS caused by GAS and by S. aureus. In GAS TSS, mortality is
higher (30 versus 3 percent with S. aureus), bacteremia and tissue necrosis are more common, and generalized erythema is less common
[71]. (See "Treatment of streptococcal toxic shock syndrome".)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The
Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key
questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short,
easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are
written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical
jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You
can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.)
Basics topics (see "Patient information: Scarlet fever (The Basics)" and "Patient information: When to worry about a fever (The Basics)")
SUMMARY
Fever with an accompanying rash is a common symptom constellation in patients presenting to clinicians' offices and emergency
departments. Skin manifestations may provide the only early clue to an underlying infection, may be the hallmark of contagious
disease, and/or may be an early sign of a life-threatening infection. The differential diagnosis of fever and rash is extremely broad, but
this symptom complex provides an opportunity for the diligent clinician to establish a probable etiology through a careful history and
physical examination. (See 'Introduction' above.)
A systematic approach is crucial for establishing a timely diagnosis, determining early therapy when appropriate, and considering
isolation of the patient if necessary. Epidemiologic clues are important to pursue such as:
Age of the patient
Season of the year
Travel history
Geographic location
Exposures including to insects, animals, and ill contacts
Medications
Immunizations and history of childhood illnesses
The immune status of the host (See 'Introduction' above.)
Features of the rash are also important to consider, including:
Characteristics of the lesions
Distribution and progression of the rash
Timing of the onset in relation to fever
Change in morphology, such as papules to vesicles or petechiae (See 'Introduction' above.)
A number of infections characterized by fever and rash have a distinct seasonal predisposition. As examples, nonpolio enteroviral
infections occur in the summer and fall months; Kawasaki syndrome, meningococcal infection, and parvoviral infections present most
commonly in the winter or early spring months; measles and rubella are more frequent in the spring; tick-borne diseases such as Lyme
disease, ehrlichiosis, and Rocky Mountain spotted fever (RMSF) primarily occur in the spring and summer; tularemia and plague are
usually seen in the summer. (See 'Season of the year' above.)
Exposures to food, water, plant materials, animals, and infected human secretions can lead to rashes and can be associated with both
occupational and nonoccupational contacts. (See 'Exposure history' above.)
A thorough sexual history is essential in evaluating the patient with a rash of unknown etiology. Genital or rectal ulcerations may be
caused by a variety of infectious agents, including syphilis (picture 18), herpes simplex (picture 19), lymphogranuloma venereum
(picture 20), chancroid (picture 21), and donovanosis (picture 22 and table 2A-B). (See 'Sexual history' above.)
The diagnostic approach to the patient with fever and rash should focus on the appearance of the rash in addition to the detailed
epidemiologic history listed above. (See 'Diagnostic approach' above.)
A history of the rash should include the following questions:
Was a prodrome present?
Where and when did the rash start?
How has the rash progressed anatomically?
Has the rash changed in appearance?
Has any treatment been instituted for the rash? (See 'Characteristics of the rash' above.)
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In examining a rash, it is essential to characterize the lesions, both individually and collectively, according to morphology and
arrangement (annular, linear, serpiginous, dermatomal, etc), distribution (isolated versus generalized, bilateral versus unilateral,
symmetric, occurring on exposed areas, etc), and evolution (centrifugal versus centripetal). In addition, a differential diagnosis for fever
and rash can be based upon the appearance of the rash and its accompanying signs (table 3A-C and table 4A-B). (See 'Characteristics
of the rash' above.)
Appropriate laboratory testing includes:
Nonspecific tests such as complete blood count and urinalysis
Blood cultures, including specific media and isolation methods for work-up of bacteria, mycobacterial, and fungal organisms
should be inoculated prior to beginning antimicrobial therapy
Serologic tests, when appropriate (eg, for Coccidioides immitis, hepatitis B, Toxoplasma gondii, Borrelia burgdorferi, Treponema
pallidum, dengue fever, and HIV).
Antigen tests, when appropriate (eg, serum cryptococcal antigen) (see 'Laboratory testing' above)
Fluid from vesicular, pustular, petechial, ulcerative, and bullous lesions can be examined. Vesicular lesions should be unroofed so that
the base of the lesion can be swabbed; herpes simplex virus and varicella-zoster virus can be distinguished with rapid fluorescent
antibody studies. Viral culture can also be performed. Aspirated fluid from pustules and bullous lesions should be Gram stained and
cultured by the microbiology laboratory. (See 'Laboratory testing' above.)
Skin biopsy can be particularly useful in establishing a diagnosis for nodular lesions but can also be obtained for petechial-purpuric,
maculopapular, and ulcerative rashes. Biopsy material should be sent to the microbiology and pathology laboratories for appropriate
culture and histopathologic evaluation. (See 'Laboratory testing' above.)
Several infections associated with fever and rash constitute emergencies that must be recognized promptly by the evaluating clinician.
Such infections include meningococcal infection, bacterial endocarditis, Rocky Mountain spotted fever, and toxic shock syndrome. (See
'Selected fever and rash emergencies' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
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71. Stevens DL. The toxic shock syndromes. Infect Dis Clin North Am 1996; 10:727.
72. Schlievert PM, Shands KN, Dan BB, et al. Identification and characterization of an exotoxin from Staphylococcus aureus associated
with toxic-shock syndrome. J Infect Dis 1981; 143:509.
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GRAPHICS
Measles exanthem

Blanching erythematous rash with some confluent areas on the trunk


in a patient with measles.
Copyright Dr. Michael Bennish; reproduced with his permission.
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Primary varicella lesions

Vesicular lesions on an erythematous base are characteristic of


chickenpox. The lesions occur in crops and are present in a variety of
stages from maculopapular to vesicular or even pustular. Central
necrosis and early crusting is also visible.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995.

http://www.lww.com
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Erythema infectiosum

Reticulating pattern of an erythematous eruption on the extremities


due to parvorvirus B19. Rash is more common in children. The
presence of intense erythema (a slapped cheek appearance) on the
face is highly characteristic.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Strawberry tongue

Reproduced with permission from: www.visualdx.com. Copyright Logical


Images, Inc.
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Rash in infectious mononucleosis

A generalized, erythematous, maculopapular eruption is often seen in


patients with infectious mononucleosis after the administration of
ampicillin.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Dermatomal herpes zoster

Grouped vesicles on an erythematous base present in a dermatomal


distribution on the upper back due to Herpes zoster. The lesions stop
abruptly at the midline.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Cutaneous leishmaniasis

Nodular lesion with central ulceration found on the arm of a patient


with cutaneous leishmaniasis. Fever is typically absent and a history
of travel can usually be obtained.
Courtesy of Charles V Sanders. The Skin and Infection: A Color Atlas and
Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Romaas sign

Unilateral eyelid edema is the Romaa's sign of Trypanosoma cruzi


infection. This agent causes Chagas' disease and is found in Central
and South America.
Courtesy of Joy D Jester, Rolando E Saenz, Lee T Nesbitt, Jr, and WA Krotoski.
The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr
(Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Skin lesion of cutaneous larva migrans

Characteristic elevated, serpiginous, reddish-brown lesion of


cutaneous larva migrans as the larvae migrate at a rate of several
millimeters per day.
Courtesy of Peter F Weller, MD.
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Onchocerciasis

A painless subcutaneous nodule (arrow) inhabited by the adult filarilal


worms of Onchocerca volvulus which is transmitted by the black fly.
The female adult worms give rise to the microfilariae that produce the
dermal and ocular manifestations of onchocerciasis.
Courtesy of Krotoski WA. The Skin and Infection: A Color Atlas and Text,
Sanders, CV, Nesbitt, LT Jr (Eds), Williams &Wilkins, Baltimore 1995.

http://www.lww.com
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Incubation period for infectious diseases associated with fever and rash
Agent/disease

Incubation period

Arcanobacterium haemolyticum

Unknown

Atypical measles

7 to 14 days

Blastomyces dermatitidis

30 to 45 days

Boutonneuse fever (Rickettsia conorii)

6 to 10 days

Cat scratch disease

7 to 14 days

Chancroid

1 to 35 days

Chickenpox

10 to 20 days

Chlamydia psittaci

5 to 21 days

Coccidioides immitis

7 to 21 days

Coxsackie/echovirus

2 to 9 days

Cutaneous larva migrans

2 to 4 days

Dengue

3 to 14 days

Disseminated gonococcal infection

5 days to several months

Ehrlichiosis

7 to 21 days

Escherichia coli 0157:H7

3 to 8 days

Epstein-Barr virus (mononucleosis)

30 to 50 days

Gnathostomiasis

3 to 12 months

Granuloma inguinale

8 to 80 days

Hepatitis B

45 to 160 days

Hepatitis C

14 to 180 days

Herpes simplex (genital)

2 to 7 days

Human immunodeficiency virus (HIV)

28 to 180 days

Kawasaki syndrome

Unknown

Leishmaniasis

14 to 56 days

Loiasis

6 to 12 months

Lyme disease

3 to 30 days

Lymphogranuloma venerum (LGV)

3 to 21 days

Mycobacterium leprae

>1 year

Mycobacterium marinum

14 to 56 days

Adapted with permission from Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas
and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995.
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Incubation period for infectious diseases associated with fever and rash
Agent/disease

Incubation period

Mycoplasma pneumoniae

7 to 28 days

Neisseria meningitidis

1 to 10 days

Onchocerciasis

6 to 12 months

Parvovirus B19

7 to 21 days

Reiter's syndrome

7 to 14 days

Relapsing fever

4 to 18 days

Rheumatic fever

7 to 35 days

Rickettsialpox, Rickettsia akari

10 to 14 days

Rocky Mountain spotted fever, Rickettsia rickettsii

2 to 14 days

Roseola infantum

5 to 15 days

Rubella

5 to 21 days

Rubeola

10 to 14 days

Salmonella typhi (enteric fever)

3 to 60 days

Spirillum minus

7 to 24 days

Sporothrix schenckii

7 to 30 days

Staphylococcal toxic shock syndrome

2 days

Streptobacillus moniliformis

3 to 22 days

Syphilis

9 to 90 days

Toxoplasma gondii

4 to 21 days

Trypanosoma cruzi

5 to 14 days

Tularemia

1 to 21 days

Typhus: endemic flea-borne, Rickettsia typhi

7 to 14 days

Typhus: epidemic louse-borne, Rickettsia prowazekii

7 to 14 days

Typhus: scrub, Rickettsia orientalis/Rickettsia tsutsugamushi

6 to 21 days

Vibrio vulnificus

1 to 4 days

Yersinia pestis

2 to 8 days

Adapted with permission from Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas
and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995.
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Herpetic whitlow

In addition to erythema, swelling, and pain, herpetic whitlow is


characterized by the presence of vesicular or pustular lesions.
Patients may also experience fever, lymphadenitis, and epitrochlear or
axillary lymphadenopathy.
Reproduced with permission from: Nikkels AF, Peirard GE. Treatment of
mucocutaneous presentations of herpes simplex virus infections. Am J Clin
Dermatol 2002; 3:479. Copyright 2002 Adis International.
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Cat scratch disease

This patient with cat scratch disease has a primary inoculation lesion
and prominent cervical lymphadenopathy (arrow).
Courtesy of Joy D Jester. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Ulceroglandular tularemia

The primary inoculation site in this patient with ulceroglandular


tularemia is an ulcerated nodule that is accompanied by
lymphadenopathy.
Courtesy of Charles V Sanders. (The Skin and Infection: A Color Atlas and
Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Erysipeloid

Erysipeloid is the localized cutaneous form of the infection caused by


Erysipelothrix rhusiopathiae. In this patient, violaceous maculopapular
lesions of the fingers developed after cleaning fish.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Lymphocutaneous sporotrichosis

Lymphocutaneous sporotrichosis on the right lower extremity of a


young man who overturned his dirt bike and inoculated soil in multiple
places in his leg. Following a plastic surgery procedure before the
diagnosis of sporotrichosis, new lesions developed at the edge of the
skin graft and extended up into the thigh.
Courtesy of Carol A. Kauffman, MD.
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Erythema migrans

Erythema migrans with central clearing and a necrotic center.


Courtesy of Dori F Zaleznik, MD.
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Hot tub folliculitis

This form of folliculitis is caused by Pseudomonas aeruginosa and can


occur after exposure to hot tubs or whirlpools.
Courtesy of Charles V Sanders. The Skin and Infection: A Color Atlas and
Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Primary syphilis

Primary chancre on the labia majora. Chancres are painless and


frequently can be missed, especially in women.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Genital herpes

Multiple grouped vesicles of genital herpes on the shaft of the penis.


These lesions are frequently painful.
Courtesy of Larry Millikan. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Lymphogranuloma venereum

A dramatic case of lymphogranuloma venereum shows chronic


ulcerating lymph nodes and prominent edema.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Chancroid ulcer on penis

Penile ulcer due to chancroid which is accompanied by marked inguinal


lymphadenitis
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Donovanosis

Numerous ulcerogranulomatous, friable lesions are visible in the


inguinal area and on the scrotum in a patient with donovanosis.
Courtesy of Lee T Nesbitt, Jr.; The Skin and Infection: A Color Atlas and Text,
Sanders, CV, Nesbitt, LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
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Characteristics of sexually transmitted genital ulcers


Primary
syphilis

Genital herpes

Chancroid

Lymphogranuloma
venereum

Donovanosis

Etiology

Treponema
pallidum

Herpes simplex

Haemophilus
ducreyi

Chlamydia trachomatis

Calymmatobacterium
granulomatis

Incubation

9 to 90 days;

2 to 7 days

Range 1 to 35

3 days to 3 weeks;

Precise data

period

average 2 to 4
weeks

days; average
3 to 7 days

average 10 to 14 days

unavailable;
probably a few days
to several months

Number of
lesions

Usually single
lesion, but
multiple lesions

Multiple; may
coalesce; more
lesions appear in

Usually 1 to 3,
but multiple
lesions may

Usually single

Single or multiple

may occur

primary episodes
than in

occur

recurrences
Appearance
of genital

Sharply
demarcated

Small superficial
grouped vesicles

Deep, sharply
demarcated

Papule, pustule,
vesicle, or ulcer;

Sharply defined
irregular ulcerations

ulcers

round or oval
ulcer with
slightly

and/or erosions;
lesions may
coalesce, forming

ulcer; irregular
ragged
undermined

discrete and transient;


frequently overlooked.

or hypertrophic,
verrucous, necrotic,
or cicatrical

elevated
edges; may be
irregular or

bullae or large
areas of
ulceration;

edge; ranges
in diameter
from a few ml

symmetrical
("kissing

lesions have
irregular borders.

to 2 cm.

Bright, red, and


smooth.

Rough, uneven,
yellow to gray

granulomas.

chancre").
Base

Red, smooth
and shiny, or
crusted; serous
exudate occurs
when

Variable.

in color.

granulations; can
be necrotic,
verrucous, or

squeezed.
Induration

Firm; does not


change shape
with pressure.

Usually friable,
rough, beefy

cicatrical.
None.

Soft; changes
shape with

None.

Firm granulation
tissue.

pressure.

Adapted with permission from Martin DH, Mroczkowski TF: Sexually Transmitted Diseases. In: The Skin and Infection: A Color
Atlas and Text. Sanders CV, Nesbitt LT (Eds). Baltimore, Maryland: Williams & Wilkins, 1995, p. 95.
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Characteristics of sexually transmitted genital ulcers


Primary syphilis
Pain

Genital herpes

Painless; may

Common; more

become tender if
secondarily infected.

prominent with initial


infection than with

Chancroid

Lymphogranuloma
venereum

Donovanosis

Common

Variable

Rare

recurrences.
Inguinal
lymphadenopathy

Unilateral or
bilateral; firm,

Usually bilateral,
firm, and tender;

Unilateral
(rarely

Unilateral or bilateral;
initially movable, firm,

Pseudobuboes;
subcutaneous

movable, and
nontender; do not
suppurate.

more common in
primary episodes
than in recurrences.

bilateral);
overlying
erythema;

and tender; later


indolent; fixed and
matted; "sign of

perilymphatic
granulamotous
lesions that

matted,
fixed, and

Groove" may
suppurate; fistulas.

produce
inguinal

tender; may
suppurate.
Constitutional

Rare

symptoms

Rare

Frequent

Rare

May

Local lesions heal;

Worsens

progress to
erosive

systemic disease may


progress;

slowly.

lesions.

disfigurement; late
complications.

episode; less likely


in recurrences.

Course of

Slowly resolves to

disease if
untreated

latency (2 to 6
weeks).

Diagnostic tests

Common in primary

swelling.

Typically recurs.

Darkfield exam,

Tzanck smear,

Culture,

Lymphogranuloma

"Donovan

direct
immunofluorescence,
FTA-ABS, VDRL.

culture, Pap smear,


direct
immunofluorescence,

biopsy
(rarely
done); Gram

venereum (LGV)
complement fixation
test; isolation of the

bodies" in
tissue smears;
biopsy.

electron-microscopy,
direct

stained
smears have

microorganism by
culture.

immunoperoxidase
staining, serology.

low
specificity.

Adapted with permission from Martin DH, Mroczkowski TF: Sexually Transmitted Diseases. In: The Skin and Infection: A Color
Atlas and Text. Sanders CV, Nesbitt LT (Eds). Baltimore, Maryland: Williams & Wilkins, 1995, p. 95.
Graphic 68988 Version 2.0

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Secondary syphilis

Maculopapular rash on the palms, which rarely can be pustular, in a


patient with secondary syphilis. Patients can be quite contagious at
this stage.
Courtesy of David H Martin and Tomasz F Mroczkowski. The Skin and
Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams &
Wilkins, Baltimore, 1995.

http://www.lww.com
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Condyloma lata

Flat condyloma lata lesions which are moist in a woman with


secondary syphilis.
Courtesy of David H Martin and Tomasz F Mroczkowski. The Skin and
Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams &
Wilkins, Baltimore, 1995.

http://www.lww.com
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Tertiary syphilis

Noduloulcerative lesions in a ring-like distribution on the posterior


thigh, known as lues maligna, in a patient with tertiary syphilis.
Courtesy of David H Martin and Tomasz F Mroczkowski. The Skin and
Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams &
Wilkins, Baltimore, 1995.

http://www.lww.com
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Differential diagnosis of fever and rash based upon appearance of the rash
Macules, papules,
nodules, or plaques

Vesicles,

Purpuric macules,

Followed widespread

bullae, or

purpuric papules, or

erythema with or without

pustules

purpuric vesicles

edema by desquamation

Bacterial
Arcanobacterium

Bacillus

haemolyticum

anthracis

Bacillus anthracis

Ehrlichia canis

Bartonella bacilliformis

Listeria

Bartonella henselae (cat


scratch disease)
Bartonella quintana
(trench fever)
Borrelia burgdorferi
(Lyme disease)*
Borrelia spp (relapsing
fever)
Brucella spp
(brucellosis)*
Calymmatobacterium
granulomatis
(donovanosis)*

Bacteremia
Borrelia spp
Clostridium spp

monocytogenes

Infective endocarditis (many


species)

Mycoplasma
pneumoniae

Haemophilus influenzae type B

Neisseria
gonorrhoeae*
Neisseria
meningitidis*
Pseudomonas
aeruginosa
Rickettsia akari
Rickettsia
rickettsii*
Staphylococcus

Neisseria meningitidis (acute


or chronic
meningococcemia)*

Pseudomonas aeruginosa
Rickettsia prowazekii
Rickettsia rickettsii
Spirillum minor
Staphylococcus aureus

Ehrlichiosis*

Streptococcus
group A

Streptobacillus moniliformis

Human granulocytic
erlichiosis (HGE)
Erysipelothrix
rhusiopathiae
(erysipeloid)

pallidum
(secondary
syphilis)
Vibrio vulnificus

Stapylococcus aureus (toxic shock


syndrome [TSS], scalded skin
syndrome [SSSS])

(disseminated gonococcal
infection)*

aureus (TSS,
SSSS)

Treponema

streptococcal toxic shock syndrome)

Neisseria gonorrhoeae

Chlamydia psittaci
(psittacosis)

Ehrlichia chafeensis
(HME)

Streptococcus group A (scarlet fever,

(bacteremia)

Streptococcus group A
(streptococcal toxic shock
syndrome, scarlet fever)
Streptococcus pneumoniae
(asplenic patient)
Vibrio vulnificus
Yersinia pestis

Francisella tularensis
(tularemia)
Listeria monocytogenes
Leptospira sp
(leptospirosis)*
Mycobacterium leprae*
Mycobacterium
marinum*
Mycobacterium
tuberculosis
Mycoplasma pneumoniae
Neisseria gonorrhoeae
(gonorrhea)*
Neisseria meningitidis
(meningococcemia)*
Pseudomonas
aeruginosa
Rickettsia akari

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(rickettsialpox)
Rickettsia prowazekii
(epidemic/louse-borne
typhus)
Rickettsia rickettsii

(RMSF-early lesions)*
Rickettsia
orientalis/tsutsugamushi
(scrub typhus)
Rickettsia typhi
(endemic/murine
typhus)
Salmonella typhi
(typhoid fever)*
Spirillum minor (rat-bite
fever)
* Reportable disease.
May have arthralgia or musculoskeletal pain.
Specific therapy available.
Adapted with permission from: Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color
Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. Originally modified with permission from
Fitzpatrick TB, et al: Color Atlas & Synopsis of Clinical Dermatology - Common and Serious Diseases. Fitzgerald TB, et al (Eds),
McGraw-Hill, New York, 1992.
Graphic 52167 Version 6.0

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Differential diagnosis of fever and rash based upon appearance of the rash
Macules, papules,
nodules, or plaques

Vesicles,

Purpuric macules,

Widespread erythema with

bullae, or

purpuric papules, or

or without edema followed

pustules

purpuric vesicles

by desquamation

Fungal
Blastomyces dermatitidis*
Candida spp

Histoplasma
capsulatum

Coccidioides immitis
Cryptococcus neoformans
Histoplasma capsulatum
Other disseminated deep
fungal infections in
immunocompromised
patients
Viral
Adenovirus
Arbovirus
Atypical measles*
Colorado tick fever
Coxsackieviruses A and B
Cytomegalovirus, primary
infection

Colorado tick
fever

Atypical measles*

Coxsackie A5, 9,
10, 16, B2, 7

Colorado tick fever

Echoviruses

Congenital
cytomegalovirus

Eczema

herpeticum

Dengue virus

Herpes simplex
(disseminated)

Epstein-Barr virus, primary

Varicella

infection

(chickenpox)

Echoviruses

Varicella-zoster

Hepatitis B (urticaria)*

Adenovirus (rare)

(disseminated)

Human herpesvirus 6
(exanthem subitum)*

Kawasaki syndrome (presumed


viral)

Coxsackie A and B (rare,


types A-9, B2-5)
Dengue fever
Epstein-Barr virus (rare)
Echoviruses (rare, types 3,
4, 9)
Rubella*
Varicella zoster virus
Yellow fever

Human immunodeficiency
virus (HIV-1)*
Kawasaki syndrome
(presumed viral)
Molluscum contagiosum
Orf
Parvovirus B19 (erythema
infectiosum [fifth disease])
Rubella (German measles)*
Rubeola (measles)*
Varicella (chickenpox)*
Varicella zoster
(disseminated)
Viral hemorrhagic fevers
(many)
* Reportable disease.
May have arthralgia or musculoskeletal pain.

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Umbilicated papule or vesicle a characteristic of these exanthems.


Adapted with permission from: Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color
Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. Originally modified with permission from
Fitzpatrick TB, et al: Color Atlas & Synopsis of Clinical Dermatology - Common and Serious Diseases. Fitzgerald TB, et al (Eds),
McGraw-Hill, New York, 1992.
Graphic 63955 Version 4.0

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Differential diagnosis of fever and rash based upon appearance of the rash

Macules, papules,

Vesicles, bullae, or

nodules, or plaques

pustules

Purpuric macules,
purpuric papules, or
purpuric vesicles

Widespread erythema
with or without
edema followed by
desquamation

Protozoal/parasitic
Leishmania braziliensis

Plasmodium falciparum
(blackwater fever)*

Leishmania mexicana

Trichinella spiralis

Leishmania tropica

(trichinosis)

Necator americanus

Toxoplasma gondii

Onchocerca volvulus
Schistosoma
Strongyloides stercoralis
Toxoplasma gondii
(toxoplasmosis)
Trichinella spiralis
(trichinosis)
Trypanosoma sp
Noninfectious
Erythema multiforme
Systemic lupus

Erythema multiforme
bullosum

erythematosus

Toxic epidermal necrolysis

Dermatomyositis

Dermatitis from plants

Drug hypersensitivities

Drug hypersensitivities

Gianotti-Crosti syndrome
Inflammatory bowel

"Allergic" vasculitis

Erythroderma

Erythroderma

Drug hypersensitivities

Cholesterol embolization

Graft-versus-host reaction

Disseminated intravascular

Stevens-Johnson syndrome

coagulation (purpura
fulminans)

Drug hypersensitivities

disease

Fat embolism

Pityriasis rosea (fever


rare)

Henoch-Schnlein purpura

Sarcoidosis

Immune thrombocytopenic
purpura

"Serum sickness"

Granulomatosis with

Sweet syndrome (acute

Toxic epidermal necrolysis


von Zumbusch pustular
psoriasis

polyangiitis (Wegener's)

febrile neutrophilic
dermatosis)
Still's disease (juvenile
idiopathic arthritis)
* Reportable disease.
May have arthralgia or musculoskeletal pain.

Often present as infarcts.


Adapted with permission from: Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color
Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. Originally modified with permission from:
Fitzpatrick TB, et al: Color Atlas & Synopsis of Clinical Dermatology - Common and Serious Diseases. Fitzgerald TB, et al (Eds),
McGraw-Hill, New York, 1992.
Graphic 71663 Version 8.0

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Differential diagnosis of fever and rash based upon accompanying signs


Arthritis or arthralgia

Desquamation

Acute meningococcemia

Arcanobacterium

Allergic purpura
Disseminated gonococcal
infection
Erythema marginatum (acute
rheumatic fever)
Hepatitis B virus, prodromal
phase

haemolyticum infection
Drug hypersensitivity
Graft-versus-host
reaction
Kawasaki syndrome
Measles

Lyme disease

Rocky Mountain spotted


fever

Parvovirus B19

Scarlet fever

Reiter's syndrome
Rocky Mountain spotted fever
Roseola (especially in adults)
Rubella
Serum sickness

Staphylococcal scaldedskin syndrome


Stevens-Johnson
syndrome
Toxic epidermal
necrolysis

Still's disease

Toxic shock syndrome

Systemic lupus

von Zumbusch pustular


psoriasis

erythematosus

Lymphadenopathy
Cervical

Meningitis
Acute meningococcemia

Kawasaki syndrome

Cryptococcosis

Rubella

Enterovirus

Scarlet fever
Generalized
Infectious
mononucleosis
Secondary syphilis
Serum sickness

(Coxsackieviruses,
echoviruses)
Leptospirosis
Lyme disease
Rocky Mountain spotted
fever
Secondary syphilis

Sarcoidosis
Systemic lupus
erythematosus
Toxoplasmosis
Hilar
Atypical measles
Sarcoidosis
Local
Cat-scratch disease
Tularemia

Adapted with permission from Adapted with permission from Sanders CV. Diagnosis of the patient with fever and rash. In: The
Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. With permission
from Hurst JW (Ed). Medicine for the Practicing Physician., 3rd ed, Butterworth-Heinemann, Boston, 1992, p. 273.
Graphic 78412 Version 2.0

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Differential diagnosis of fever and rash based upon accompanying signs


Mucosal membrane lesions
(enanthems)

Palm-sole involvement

Pulmonary infiltrate

Herpes simplex

Acute meningococcemia

Atypical measles

Infectious mononucleosis (palatal

Atypical measles

Coccidioidomycosis

Dengue

Cryptococcosis

Drug rash

Fat embolism

Erythema multiforme

Histoplasmosis

Hand-foot-mouth disease

Mycoplasma pneumoniae

Kawasaki syndrome

North American
blastomycosis

petechiae)
Measles (Koplick's spots)
Strawberry tongue
Atypical measles
Kawasaki disease
Scarlet fever
Toxic shock syndrome

Varicella zoster

Ulcerative or vesicular stomatitis


Hand-foot-mouth disease
Herpes simplex
Histoplasmosis
Inflammatory bowel disease
Secondary syphilis
Systemic lupus erythematosus

Measles
Rocky Mountain spotted fever
Secondary syphilis
Staphylococcus aureus endocarditis

Rash predominantly on
extremities

Psittacosis
Rocky Mountain spotted
fever
Sarcoidosis
Varicella zoster

Allergic purpura
Brucellosis
Disseminated gonococcal infection
Ecthyma gangrenosum
Erythema nodosum
Sporotrichosis (fever rare)

Adapted with permission from Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas
and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. With permission from Hurst JW (Ed). Medicine for
the Practicing Physician, 3rd ed, Butterworth-Heinemann, Boston, 1992, p. 273.
Graphic 54445 Version 2.0

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Erythema multiforme

Characteristic target lesions of the palm in erythema multiforme begin


with a central vesicle.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995.

http://www.lww.com
Graphic 74095 Version 5.0

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Causes of erythema multiforme


Contact reactions
Tadania ignis (fire sponge)

Drugs
Allopurinol
Antituberculous agents
Barbiturates
Carbamazepine
Oral hypoglycemic agents
NSAIDs
Phenytoin
Sulfonamides

Endocrine factors
Pregnancy

Idiopathic
>50 percent

Infections
Epstein-Barr virus
Francisella tularensis
Hemolytic streptococci
Herpes simplex 1 and 2
Histoplasma capsulatum
Mycoplasma pneumoniae
Mycobacterium tuberculosis
Proteus sp
Salmonella sp
Staphylococcus sp
Vibrio parahaemolyticus
Yersinia sp

Physical
Sunlight
X-ray therapy
Adapted with permission from Sanders CV, Diagnosis of the Patient with Fever and Rash. In: The Skin and Infection: A Color
Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. Originally modified with permission from
Dermatology in General Medicine, Fitzpatrick TB, et al (Eds), McGraw-Hill, New York, 1993.
Graphic 72248 Version 2.0

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Erythema nodosum

Painful erythematous nodules of erythema nodosum are often found in


a symmetric distribution on the legs. The nodules can also appear to
be pigmented.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore. 1995.

http://www.lww.com
Graphic 80056 Version 5.0

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Toxic epidermal necrolysis

Usually caused by drugs, toxic epidermal necrolysis demonstrates


widespread erythema and confluent vesiculation, leading to sloughing
of the skin. Affected patients are at risk for hypernatremic
dehydration and sepsis.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
Graphic 66134 Version 5.0

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Causes of toxic epidermal necrolysis


Drugs

Infections

Alka-Seltzer

Aspergillosis (pulmonary)

Allopurinol*

Escherichia coli (septicemia)

Amiodarone

Herpes simplex virus

Antibiotics, esp. tetracyclines and penicillin*

Measles virus

Anticonvulsants*

Varicella zoster virus

Antipyrine

Miscellaneous

Barbiturates*

Graft-versus-host disease

Brompheniramine
Chlorpromazine
Dapsone
Ethambutol
Fansidar
Fenoprofen
Gold
Griseofulvin
Ipecac
Isoniazid
NSAIDs
Pentamidine

Idiopathic

Neoplasia
Hodgkin's disease
Leukemia
Non-Hodgkin's lymphoma

Vaccinations
BCG
Diphtheria toxoid
Measles
Poliomyelitis
Tetanus antitoxin

Phenolphthalein
Quinine
Streptomycin
Sulfonamides*
Tolbutamide
Trimethoprim
* Most commonly associated with toxic epidermal necrolysis (TEN).
Adapted with permission from Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas
and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. With permission from Rohrer TE, Ahmed AR. Toxic
epidermal necrolysis. Int J Dermatol 1991; 30:457.
Graphic 65062 Version 3.0

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Giant urticaria

Very large erythematous annular lesion of the shoulder with central


clearing. This patient had several large lesions of this type which
could be confused with erythema migrans.
Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
Graphic 81678 Version 3.0

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Infectious agents and illnesses associated with urticaria


Agent

Illness

Bedbugs, kissing bugs, ants, fleas, flies, and mosquitoes

Bites and stings

Coxiella burnetii

Q Fever

Coxsackieviruses A9, A16, B4, B5

Rash

Echinococcus sp

Echinococcosis

Echovirus 11

Rash

Epstein-Barr virus

Infectious mononucleosis

Entamoeba histolytica

Amebiasis

Enterobius vermicularis

Pinworm infestation

Giardia lambdia

Giardiasis

Hepatitis B virus

Hepatitis B

Mites

Bites

Mumps virus

Mumps

Mycoplasma pneumoniae

Atypical pneumonia

Necator americanus

Hookworm disease

Neisseria meningitidis

Meningococcemia

Plasmodium sp

Malaria

Pediculus humanus

Pediculosis

Sarcoptes scabiei

Scabies

Schistosoma sp

Schistosomiasis

Shigella sonnei

Shigellosis

Trichinella spiralis

Trichinosis

Trichobilharzia sp

Swimmer's itch; collector's itch

Trichomonas vaginalis

Vulvovaginitis

Trombicula irritans

Chigger bites

Wuchereria bancrofti

Filariasis

Yersinia enterocolitica

Yersiniosis

Adapted with permissiom from Sanders CV, Diagnosis of the Patient with Fever and Rash. In: The Skin and Infection: A Color
Atlas and Text. Sanders CV, Nesbitt LT (Eds), Baltimore, Maryland: Williams & Wilkins, 1995. Originally modified from Textbook of
Pediatric Infectious Diseases, 3rd ed, Vol 1, Feigin RD and Cherry JD (Eds), Philadelphia, WB Saunders, Philadelphia 1992, p. 771.
Graphic 74764 Version 2.0

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Purpura fulminans

Skin lesions in acute meningococcemia can begin as papules but


quickly progress to petechiae and purpura. As seen here, the purpuric
lesions can coalesce.
Courtesy of Charles V Sanders. (The Skin and Infection: A Color Atlas and
Text, Sanders, CV, Nesbitt, LT Jr (Eds), Williams & Wilkins, Baltimore, 1995).
Graphic 52107 Version 2.0

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Subconjunctival petechiae in infective endocarditis

Subconjunctival petechiae are prominent in this case of bacterial


endocarditis caused by Staphylococcus aureus.
Courtesy of Jan V Hirschmann. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
Graphic 59982 Version 6.0

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Splinter hemorrhages in infective endocarditis

Splinter hemorrhages, linear reddish-brown lesions, are seen in the nail


bed of this patient with bacterial endocarditis due to group B
Streptococcus.
Courtesy of Gene Beyt. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995.

http://www.lww.com
Graphic 72076 Version 9.0

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Janeway lesion in infective endocarditis

A Janeway lesion (arrow) occurred on the palm in this patient with


bacterial endocarditis due to Streptococcus bovis. These lesions are
macular, nonpainful, and erythematous; they are located on the palms
and soles.
Courtesy of Jan V Hirschmann. The Skin and Infection: A Color Atlas and Text,
Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995.

http://www.lww.com
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Osler's nodes in infective endocarditis

Osler's nodes are tender papulopustules located on the pulp of the


finger in a patient with bacterial endocarditis caused by
Staphylococcus aureus.
Courtesy of Charles V Sanders. The Skin and Infection: A Color Atlas and
Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995.

http://www.lww.com
Graphic 68796 Version 8.0

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Rocky mountain spotted fever

Extensive maculopapular and petechial lesions on the trunk and thigh


in a patient with Rocky Mountain spotted fever. The rash
characteristically begins on the wrists and ankles and spreads
centripetally.
Courtesy of Harold G Muchmore. The Skin and Infection: A Color Atlas and
Text, Sanders CV, Nesbitt LT Jr (Eds), Williams &Wilkins, Baltimore, 1995.

http://www.lww.com
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Rash in Staphylococcal toxic shock syndrome

Erythematous maculopapular eruption on the abdomen in a patient


with staphylococcal toxic shock syndrome (TSS). The erythroderm of
TSS can be subtle and resemble a sunburn.
Courtesy of Charles V Sanders. The Skin and Infection: A Color Atlas and
Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
Graphic 77600 Version 4.0

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Conjunctival suffusion in Staphylococcal toxic shock


syndrome

Conjunctival suffusion in a patient with staphylococcal toxic shock


syndrome (TSS).
Courtesy of Charles V Sanders. The Skin and Infection: A Color Atlas and
Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com
Graphic 66457 Version 4.0

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