Many illnesses caused by infectious agents have associated cutaneous manifestations. In some cases, the exanthem may be the hallmark of the disease; in others, it may be only a vague indicator of a more significant underlying process. When an exanthem occurs, it often offers important clues to the etiology of a patient’s illness. Although most exanthematous illnesses in children are benign, their differential diagnosis is critical because the early manifestations of potentially fatal bacterial and rickettsial diseases frequently have cutaneous findings.
History
Exanthematous manifestations of infectious illnesses have been important since medical antiquity. Major epidemics of both measles and smallpox occurred in the Roman Empire and in China at the beginning of the Christian era. Scarlet fever was recognized as a distinct entity in the 17th century, and chickenpox and rubella were identified in the 18th and 19th centuries, respectively.
In the writings of the early 20th century, maculopapular exanthematous illnesses of children frequently were referred to by number. Scarlet fever and measles historically were the first two classic maculopapular exanthems of childhood. Which one had the honor of being the “first disease” is unknown today. The “third disease” was rubella, which was recognized by the beginning of the 20th century as a distinct entity. In 1900, Dukes described an exanthematous illness with the characteristics of both rubella and scarlet fever, which he suggested was a “fourth disease.” The general opinion today is that his disease was not a distinct entity. Shaw suggested that Dukes’ cases had mild atypical scarlet fever, and Powell raised the possibility that the illness resulted from epidermolytic toxin–producing staphylococci. My opinion has been that probably rubella and scarlet fever both were epidemic in the student population under Dr. Dukes’ care; combined infections led to the confusion. In 1991, Morens and Katz came to the same conclusion.
Erythema infectiosum (see Chapter 152 ) commonly is referred to as the fifth disease, and roseola infantum (see Chapter 59 ) qualifies as the sixth disease.
During the past 65 years, interest in exanthematous diseases has been renewed because a large number of previously unknown viruses and other infectious agents that cause cutaneous manifestations have been discovered. In addition, the pattern of disease caused by classic exanthem-producing agents has changed; smallpox has been eradicated, the epidemiology of measles and rubella has been altered by immunization, and ecologic changes have resulted in differences in viral and bacterially induced rashes.
Etiologic Agents
Many different types of viruses, chlamydiae, rickettsiae, mycoplasmas, bacteria, fungi, and protozoan and metazoan agents cause illnesses with associated cutaneous manifestations. Although this chapter is devoted to systemic infectious diseases with cutaneous manifestations, the demarcation between exanthematous disease of systemic and local origin is not always readily apparent. For example, the recurrent cold sore caused by herpes simplex virus (HSV) infection frequently is considered a local problem, although its nature and pathogenesis involve central virus latency and host systemic immune functions. Similarly superficial fungal diseases and other local infections, such as warts, may be quite dependent on more general immunologic functions of the host. The exanthems of enteroviral infections frequently are confused with those caused by insect bites and allergic problems.
Table 58.1 presents viruses that have cutaneous manifestations in humans. Erythema infectiosum is caused by human parvovirus B19. This virus also is an important cause of the papular-purpuric gloves-and-socks syndrome that is an uncommon occurrence and mainly affects young adults. Human parvovirus B19 also has been associated with a vesiculopustular exanthem, erythema multiforme, and other petechial and purpuric rashes. In one study, an erythematous maculopapular rash was noted in 9% of children with human bocavirus infections. Adenovirus types 1, 2, 3, 4, 7, and 7a have been isolated from children and young adults with exanthem. The overall clinical expression rate of exanthem in adenovirus infection rarely has been studied. Fukumi and associates noted that rash occurred in 2% of adenoviral infections, Hope-Simpson and Higgins indicated a rate of approximately 8%, and Esposito and associates noted an occurrence rate of 5.7%.
| Virus | Disease or Syndrome | Incubation Period (Days) | Main Season | Clinical Characteristics | EXANTHEM | Usual Duration (Days) | |
|---|---|---|---|---|---|---|---|
| Lesions | Distribution | ||||||
| Human parvovirus B19 | Erythema infectiosum; gloves-and-socks syndrome | 7–17 | Winter and spring | Biphasic illness with mild prodromal period with headache and malaise for 2–3 days, then 7-day symptom-free period, followed by typical exanthema | Three-stage exanthema: initially, rash on cheeks (slapped-cheek appearance) and then erythematous maculopapular rash on trunk and limbs; finally, rash develops a reticular pattern | Starts on face More prominent on extensor surfaces of extremities | 7–21 |
| Human bocavirus | Fall, winter, and spring | Fever, cough, coryza, respiratory distress (bronchitis, bronchiolitis, pneumonia) | Erythematous maculopapular | Mainly face, chest, and trunk | |||
| Human papillomaviruses | Warts | Nonseasonal | Local cutaneous disease | Papular or nodular isolated lesions | Most common on extremities | 100+ | |
| Adenovirus types 1, 2, 3, 4, 7, and 7a | 6–9 | Winter and spring | Fever and signs and symptoms of respiratory illness Occasionally, rash occurs after defervescence (roseola-like) | Most commonly erythematous, maculopapular, and discrete (rubelliform), but occasionally confluent (morbilliform) Rarely, erythema multiforme and Stevens-Johnson syndrome | Usually starts on face and spreads downward to trunk and extremities | 3–5 | |
| Herpes simplex types 1 and 2 | Cold sores, genital herpes, neonatal herpes, or other | 2–12 | Nonseasonal | Primary disease associated with fever and systemic symptoms Recurrent disease caused by exogenous and endogenous infections | Singular or grouped vesicular lesions varying in size from 2 to 10 mm, frequently on a mildly erythematous base Occasionally, erythema multiforme, Stevens-Johnson syndrome, and erythema nodosum | Lesions in primary infection with type 1 virus are mainly in and around the mouth Recurrent type 1 lesions usually perioral Primary and recurrent type 2 lesions usually on genitals | 7–14 |
| Human herpesvirus–6 (HHV-6) | Roseola infantum | Nonseasonal | Fever 3–5 days in duration, rapid defervescence, and then the appearance of rash | Erythematous macular or maculopapular | Most prominent on neck and trunk Face and extremities may be affected | 1–2 | |
| Human herpesvirus–7 (HHV-7) | Roseola infantum | Nonseasonal | Fever 3–5 days in duration, rapid defervescence, and then the appearance of rash | Erythematous macular or maculopapular | Most prominent on neck and trunk Face and extremities may be affected | 1–2 | |
| Human herpesvirus–8 (HHV-8) | Kaposi sarcoma | Months to years | Nonseasonal | Asymptomatic infection Most commonly noted in AIDS patients but occurs in other immunodeficiency states | Purple to blue nodular, raised lesions | Any epidermal or mucosal surface | Months to years |
| Varicella zoster | Chickenpox (varicella) | 12–20 | Late fall, winter, and spring | Malaise and fever of 5–6 days’ duration | Basic lesion is vesicular, but lesions go through stages: macules, papules, vesicles, and crusts Lesions occur in crops | Lesions more profuse on trunk than on extremities Proximal end of extremities more involved than distal end | 8–10 |
| Herpes zoster | Nonseasonal | Endogenous infection Pain and paresthesia with dermatome distribution | Basic lesion is vesicular, but lesions go through stages: macules, papules, vesicles, and crusts | Lesions localized to area of skin innervated by a single sensory ganglion | 10–28 | ||
| Epstein-Barr | Infectious mononucleosis | 28–49 | Nonseasonal | Fever, pharyngitis, and lymphadenopathy Exanthem occurs in 3–13% of cases If amoxicillin is administered, then exanthema in 30% of cases | Most commonly erythematous, macular, maculopapular, and discrete (rubelliform) In association with ampicillin administration, the rash may be more vivid Erythema multiforme and urticaria may occur | Mainly on trunk and proximal end of extremities | 2–7 |
| Cytomegalovirus | Cytomegalovirus mononucleosis | Nonseasonal | Acquired: mild febrile illness with lymphadenopathy Congenital: disseminated disease | Erythematous, maculopapular, and discrete Vesicular or petechial in congenital infection | Located mainly on trunk and proximal end of extremities | 2–7 | |
| Vaccinia | Roseola vaccinatum, eczema vaccinatum, vaccination “take,” or disseminated vaccinia | Nonseasonal | Illness caused by direct exposure via vaccination or exposure to a vaccinee | Vaccination and eczema vaccinatum lesions go through stages: papule, vesicle, pustule, and scab Roseola vaccinatum: erythematous maculopapular lesions Occasionally erythema multiforme Disseminated vaccinia: papular or vesicular lesions | Lesions in roseola vaccinatum, eczema vaccinatum, and disseminated vaccinia are generalized | 7–14 | |
| Variola | Smallpox | 8–17 | Seasonal by geographic area | Abrupt onset of high fever, headache, and muscle and joint pain Rash appears 2–4 days after onset | Basic lesion is vesicular, but lesions go through stages: macules, papules, vesicles, pustules, and crusts | Most prominent on exposed body surfaces Starts on extremities and face Spreads centripetally | 12–20 |
| Monkeypox | Similar to mild smallpox Exposure to monkeys No human-to-human spread | Similar to mild smallpox | Similar to mild smallpox | ||||
| Orf | Ecthyma contagiosum | 4–7 | Spring | Disease of sheep acquired by humans | Initially erythematous papule Becomes umbilicated, nodular, and then vesicular Occasionally erythema multiforme | Solitary lesion, usually on hands | 30–40 |
| Molluscum contagiosum | Molluscum contagiosum | Local cutaneous disease | Umbilicated nodular lesions: singular or clusters | Most common on face, inner aspect of thigh, breasts, and genitalia | 100+ | ||
| Paravaccinia | Milker’s nodules | 4–7 | Human infection acquired from infected calves | Nodular lesion Occasionally erythema multiforme | Solitary lesion, usually on hands | 30–40 | |
| Tanapox | A virus of monkeys Human infection associated with fever and regional lymphadenopathy | Umbilicated vesicular lesion | Upper part of body Solitary lesion | 35–56 | |||
| Coxsackieviruses A2, A4, A5, A6, A7, A9, A10, and A16; coxsackieviruses B1-B5; echoviruses 1–7, 9, 11–14, 16–19, 24, 25, 30, and 33; enterovirus 71; parechoviruses 1 and 3 | 4–7 | Summer and fall | Fever and mild to moderate pharyngitis Occasionally, herpangina, meningitis, and other manifestations of systemic viral infection Exanthem occurs in 5–50% of infections, depending on virus type Rash may occur during fever or after defervescence; hand, foot, and mouth syndrome | Most commonly erythematous, maculopapular, and discrete May have macular, petechial, vesicular, and urticarial components Rarely erythema multiforme | Usually starts on face and spreads downward to trunk and extremities May have peripheral distribution (hand, foot, and mouth syndrome) | 3–7 | |
| Rhinoviruses (many types) | 2–4 | Fall, winter, and spring | Mild fever and signs and symptoms of respiratory illness Exanthem occurs in about 5% of cases | Erythematous or maculopapular and discrete | Starts on face and spreads downward to trunk and extremities | 1–4 | |
| Foot and mouth | 3–4 | Direct animal contact Fever, sore mouth, and lymphadenopathy Vesicles and ulcers within the mouth | Vesicular lesions | Hands and feet | 3–6 | ||
| Colorado tick fever | 3–5 | Summer | Fever, chills, eye pain, myalgia, and headache Diphasic course Rash in only about 10% of cases | Occasionally maculopapular but usually petechial | Maculopapular rash is generalized Petechial rash most prominent on arms, legs, and trunk | 2–7 | |
| Reovirus 2 and 3 | 4–7 | Summer | Fever, mild pharyngitis, and cervical adenopathy | Erythematous or maculopapular Discrete or confluent Occasionally vesicular | Starts on face and spreads downward to trunk and extremities | 3–9 | |
| Rotavirus | Gianotti-Crosti syndrome; infantile acute hemorrhagic edema | 2–4 | Fall, winter, and spring | Gastroenteritis | Petechial and morbilliform | Generalized | 7–14 |
| Chikungunya, o’nyong-nyong, Ross River, Sindbis | During periods of arthropod prevalence | Fever, headache, eye pain, and marked myalgia, arthralgia, and arthritis Geographically localized diseases | Rubelliform and morbilliform Frequently vesicular and petechial | Starts on face and spreads downward to trunk and extremities | |||
| Rubella | Rubella (German measles) | 15–21 | Winter and spring | Mild symptoms with onset 1–5 days before rash Fever usually <38.5°C (101.5°F) Headache, malaise, and suboccipital and postauricular lymphadenopathy | Erythematous, maculopapular, and discrete | Starts on face and spreads downward to trunk and extremities | 4–7 |
| West Nile | Sudden onset of fever, chills, and drowsiness Rash may appear during or after fever Geographically localized disease | Erythematous, macular, and maculopapular | Starts on trunk and spreads to extremities | 3–6 | |||
| Dengue and Kunjin | 7 | During periods of specific arthropod prevalence | Sudden onset of high fever, then severe headache, myalgia, arthralgia, abdominal pain, and marked diaphoresis Fever lasts 5–6 days and ends by crisis Rash appears within 48 hours of onset of fever Geographically localized diseases | Initially, macular, flushed appearance, then erythematous, maculopapular rash May be scarlatiniform Frequently becomes petechial and purpuric Small vesicles occur in Kunjin virus infection | Initial macular rash is more prominent centrally Maculopapular rash may start on hands and feel and spread to trunk | 3–10 | |
| Influenza A and B | 2–5 | Fall, winter, and spring | Fever, cough, headache, and muscle aches and pains Usually in young children Rash an occasional occurrence | Erythematous, maculopapular, and discrete (rubelliform) Rarely erythema multiforme | Starts on face and trunk and spreads to extremities | 1–3 | |
| Respiratory syncytial | 2–5 | Fall, winter, and spring | Fever, coryza, and respiratory distress (bronchitis, bronchiolitis, or pneumonia) Usually in children <2 years | Erythematous, maculopapular, and discrete (rubelliform) | Starts on face and trunk and spreads to extremities | 1–3 | |
| Human metapneumovirus | Fall, winter, and spring | Fever, coryza, and respiratory distress (bronchitis, bronchiolitis, or pneumonia) | Erythematous, maculopapular | ||||
| Parainfluenza 1-3 | 2–5 | Fall, winter, and spring | Fever, coryza, nasopharyngitis, croup, and bronchitis Usually in young children | Erythematous, maculopapular, and discrete (rubelliform) | Starts on face and trunk and spreads to extremities | 1–3 | |
| Mumps | Mumps | 14–21 | Fall, winter, and spring | Fever, headache, and salivary gland swelling | Erythematous, maculopapular, and discrete; also, urticaria and vesicles; rarely, erythema multiforme | Most prominent on trunk | 2–5 |
| Measles | Measles | 8–12 | Winter and spring | Onset with fever, cough, coryza, and conjunctivitis | |||
| About 2 days after onset, appearance of enanthem (Koplik spots); and 2 days later, onset of exanthem | Erythematous, maculopapular, and confluent Develops a brownish appearance, and fine desquamation occurs | Starts behind ears and on forehead Spreads downward over body Confluence most prominent on face, trunk, and proximal end of extremities | 5–7 | ||||
| Lassa | Lassa fever | Sudden onset of fever, chills, headache, and sore throat Progresses to pneumonia and renal failure Geographically localized outbreaks | Macular and sometimes petechial | Localized or general | |||
| Hepatitis B | Papular acrodermatitis of childhood | 50–180 | Insidious onset with arthralgia, arthritis, and rash occurring before jaundice | Maculopapular, macular, or urticarial In young children, papular (Gianotti-Crosti syndrome or papular acrodermatitis of childhood) Rarely, erythema multiforme | Generalized | 4–10 | |
| Hepatitis C | Mixed cryoglobulinemia (not reported in children) | 7–14 | Nonseasonal | Acute hepatitis followed by chronic infection Skin findings occur late in disease | Palpable purpura | Mostly buttocks, lower extremities | Variable |
| Marburg | 5–7 | Headache, conjunctivitis, photophobia, myalgia, vomiting, diarrhea, and fever (biphasic) Exposure to vervet monkeys | Initially erythematous macular, then discrete maculopapular, and finally confluent maculopapular Exfoliation occurs Occasionally purpura | Generalized | 2–14 | ||
| Ebola | Hemorrhagic fever | 5–10 | Occurs in outbreaks | Febrile illness that progresses to hemorrhage, shock, and coma | Maculopapular rash that appears toward end of first week of illness | Lateral sides of trunk, groin, and axillae Can become generalized but spares the face | 14–60 |
| Hantavirus | Hemorrhagic fever with renal syndrome (nephropathia epidemica) | Spring and summer outbreaks | Febrile illness with hemorrhagic and renal manifestations | Flushing and petechial rash | Face (flushing), skin folds (petechiae) | 14–28 | |
| HIV | 14–60 | Nonseasonal | Fever, pharyngitis, myalgia, arthralgias, adenopathy, and rash | Macular | Mainly chest and abdomen | 7 | |
| Human T-lymphotropic virus | Infective dermatitis | Nonseasonal | Acute onset of eczema | Severe exudative eczema with a crusting, generalized, fine papular rash | Scalp, eyelid margins, perinasal skin, retroauricular areas, axillae, and groin | Months to years | |
Eight species in the Herpesvirus genus have cutaneous manifestations associated with infection, but clinical expression rates vary greatly. Nearly all primary varicella infections are associated with exanthem, whereas exanthem with acquired cytomegalovirus infection is a rare manifestation. The incidence of exanthem in Epstein-Barr virus (EBV) infection varies from 3% to 30%, depending on whether concomitant amoxicillin is administered. EBV has been associated with a unilateral laterothoracic exanthem in a 1-year-old girl and a drug-induced hypersensitivity syndrome in an 8-year-old boy. Although firm data are lacking, probably fewer than 10% of primary infections with HSV type 1 are associated with cutaneous manifestations. Erythema multiforme occasionally occurs with recurrent HSV infections. Human herpesvirus–6 (HHV-6) is a major cause of roseola infantum (see Chapter 59 ). HHV-7 also is a cause of roseola infantum ; in addition, some evidence suggests that this virus and HHV-6 may play a role in pityriasis rosea. HHV-8 infection is necessary for the development of Kaposi sarcoma in patients with acquired immunodeficiency syndrome (AIDS) and other immunodeficiency states.
At present, human illnesses with cutaneous manifestations caused by poxviruses rarely occur in the United States. Because smallpox as a disease has ceased to exist, the use of vaccinia virus for immunization has decreased dramatically. However, the terrorist events of 2001 raised concern about the possible use of smallpox virus as a terrorist weapon. Because of this potential danger, smallpox vaccines are being produced and used again. With the increased use of these vaccines, cutaneous complications of vaccinia virus infection can be expected. Monkeypox is a relatively common illness in areas of Africa (see Chapter 164 ). Outside of Africa, monkeypox, orf, and paravaccinia (milker’s nodules) continue to occur as isolated events in exposed individuals. Human infection with tanapox virus is a geographically related illness occurring in limited areas of Kenya.
In the present era, enteroviruses are the leading cause of infection-related exanthematous diseases. Thirty-eight types have been associated with rash illnesses. The clinical expression rate varies greatly among the different types; it is as high as 50% in children with coxsackievirus A16 and echovirus 9 infections. Only approximately 15% of individuals infected with echovirus 4 have exanthem, and rash is a rare occurrence in echovirus 6 infection. Hope-Simpson and Higgins noted exanthem in approximately 5% of patients with rhinoviral respiratory illness.
A young adult research worker had an influenza-like illness and a hand, foot, and mouth syndrome–like rash caused by infection with a calicivirus (San Miguel sea lion virus serotype 5) of oceanic origin.
Two percent of patients with Colorado tick fever encephalitis have exanthem. Although infection with reoviruses occurs commonly, exanthem has been noted on only nine occasions. A morbilliform rash has been observed in one adult with a rotavirus infection, and a 4-year-old boy was noted to have a petechial rash in association with a rotaviral illness. Di Lernia and Ricci described three cases of Gianotti-Crosti syndrome and one child with infantile acute hemorrhagic edema associated with rotavirus infections.
Of the Togaviridae family of viruses, rubella virus is the most important as a worldwide cause of exanthematous disease. Several alphaviruses also frequently cause exanthems. Each of these viruses has a marked geographic distribution. Similarly flaviviruses also have exanthem as part of their clinical expression, and they, too, have specific geographic boundaries. In the New York City area outbreak of West Nile virus infection in 1999, 19% of patients had exanthem. The rash was erythematous macular, papular, or morbilliform.
Exanthem generally is not considered to be a manifestation of influenza virus infection, but Hope-Simpson and Higgins noted exanthem in approximately 8% of patients from whom influenza B virus was isolated and in 1% or 2% of those infected with influenza A virus. The occurrence of Gianotti-Crosti syndrome was noted 1 week after live H1N1 influenza virus vaccination in a 9-year-old boy. Measles virus is the most notable of the Paramyxoviridae family with an associated exanthem. However, exanthem occurs rather frequently in young children infected with parainfluenza virus types 1, 2, and 3 and also in those with respiratory syncytial virus (RSV) illnesses. Hope-Simpson and Higgins noted a 15% incidence of rash in RSV infection and an approximately 15% incidence in parainfluenza virus infection. Rash, which was not described further, was observed in four children with respiratory illnesses caused by human metapneumovirus infections. Exanthem also has been noted on rare occasion with mumps virus infection.
An outbreak involving 185 cases caused by Zika virus (a flavivirus) occurred on an island in Micronesia in 2007. The patients (children and adults) had fever, macular or maculopapular exanthems, arthritis or arthralgia, and nonpurulent conjunctivitis.
Lassa fever virus, Marburg virus, Ebola virus, and hepatitis B virus all have been associated with exanthem on occasion. Rash was noted in 3 of 5 children with coronavirus OC43 lower respiratory tract infections. Hepatitis B virus is the main cause of papular acrodermatitis (Gianotti-Crosti syndrome) in children. Chronic hepatitis C virus infection occasionally causes systemic vasculitis and cryoglobulinemia in adults, with purpuric lesions concentrated on the lower extremities. Other cutaneous manifestations of chronic hepatitis C virus infection include urticaria, erythema nodosum, lichen planus, and nodular prurigo.
Hantaviruses cause two major syndromes throughout the world: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Exanthem (facial flushing and petechial lesions in skinfolds) occurs in approximately 30% of patients with hemorrhagic fever with renal syndrome, but rash is not reported in the hantavirus pulmonary syndrome. A macular rash has been noted in association with acute infection with human immunodeficiency virus type 1 (HIV-1). Several reports have associated human T-lymphotropic virus type 1 (HTLV-1) with an atypical form of eczema termed infective dermatitis. This exanthem has an acute onset and is somewhat recalcitrant to treatment.
Chlamydiae, rickettsiae, and mycoplasmas associated with cutaneous manifestations are listed in Table 58.2 . Of the chlamydiae, only Chlamydia psittaci has been associated with exanthem. In contrast, all rickettsiae that infect humans, with the exception of Coxiella burnetii, usually display some cutaneous manifestations as part of their systemic disease. Approximately 4% to 7% of adults with Q fever have exanthem. Of the mycoplasmas that infect humans, only Mycoplasma pneumoniae is associated with exanthem. In epidemics, exanthem occurs in approximately 15% of persons with respiratory illness.
| EXANTHEM | |||||||
|---|---|---|---|---|---|---|---|
| Agent | Disease or Syndrome | Incubation Period (Days) | Main Season | Clinical Characteristics | Lesions | Distribution | Usual Duration (Days) |
| Chlamydia psittaci | Psittacosis | 7–14 | Nonseasonal | Fever, chills, headache, and cough Respiratory distress | Erythematous macules Occasionally erythema multiforme or erythema nodosum | Mainly on trunk | 2–7 |
| Rickettsia akari | Rickettsialpox | 7–14 | Nonseasonal | Fever, chills, headache, backache, and malaise 4–7 days after onset of primary lesion at site of mite bite Geographically localized disease | Initial lesion at site of mite bite is papular and then vesicular, and finally an eschar forms Two days after onset of fever, erythematous maculopapular discrete rash occurs Lesions progress to small vesicles and later to scabs | Most prominent on trunk and proximal end of extremities | 7–10 |
| Rickettsia typhi | Endemic, murine typhus | 7–14 | Nonseasonal | Fever and headache Rash appears on 4th–7th day Geographically localized disease | Initially discrete macules and then erythematous maculopapular May become purpuric | Initially upper part of trunk and axilla Progresses to entire body except face, palms, and soles | 7–21 |
| Rickettsia prowazekii | Epidemic typhus | 10–14 | Nonseasonal | Sudden onset of fever, chills, headache, and myalgias Rash appears on days 4–7 Geographically localized disease | Initially discrete macules and then progresses to maculopapular and petechial lesions Sometimes purpuric | Appears first on trunk and spreads to extremities Spares palms and soles | 7–14 |
| Rickettsia tsutsugamushi | Scrub typhus | 7–21 | Nonseasonal | Sudden onset of chills, fever, and headache | Local lesion at site of chigger bite is present at onset of symptoms; characterized by vesicle, ulcer, and eschar Maculopapular rash occurs 5–8 days after onset of fever | Maculopapular rash first occurs on trunk and then becomes generalized | 7–14 |
| Rickettsia rickettsii | Rocky Mountain spotted fever | 3–12 | Summer | Abrupt onset of fever, chills, and headache Rash appears 2–4 days after onset | Early maculopapular, then petechial, and sometimes purpuric | Rash starts on distal end of extremities Rarely involves the trunk | 7–14 |
| Other tick-borne rickettsiae | Tick seasons | Similar to mild Rocky Mountain spotted fever | Similar to Rocky Mountain spotted fever; eschar at site of tick bite | Similar to Rocky Mountain spotted fever | 7–14 | ||
| R. sibirica | North Asian tick-borne rickettsiosis | ||||||
| R. australis | Queensland tick typhus | ||||||
| R. conorii | Boutonneuse fever; Mediterranean spotted fever | ||||||
| R. africae | African tick fever | ||||||
| Coxiella burnetii | Q fever | 20–40 | Nonseasonal | Acute febrile illness with chills, headache, and myalgia | Fine discrete macular rash occurring during febrile illness Transient urticarial rash also noted | Mainly on trunk | 2–7 |
| Ehrlichia and Anaplasma spp | Ehrlichiosis; anaplasmosis | 14–28 | Tick seasons | Similar to Rocky Mountain spotted fever, but rash usually not on palms and soles | Similar to endemic typhus | Similar to endemic typhus | 7–14 |
| Mycoplasma pneumoniae | 21 | All seasons | Gradual onset of fever, malaise, headache, and cough | Maculopapular rash occurs in 5–15% of cases Vesicular and bullous lesions common (Stevens-Johnson syndrome); more common in males Papular, petechial, and urticarial lesions also noted Erythema multiforme common | Rash most prominent on trunk and proximal end of extremities | 7–14 | |
In Table 58.3 , bacterial agents for which cutaneous manifestations are part of the clinical illness are presented (see Chapter 60A ). The clinical expression of exanthem varies tremendously among the different etiologic agents, as do the conditions associated with a specific infection. For example, infection with phage group 2 staphylococci usually results in cutaneous disease in young infants, whereas the same organisms rarely cause illness in adults. Symptomatic infection with Streptococcus pneumoniae is associated with cutaneous manifestations only occasionally; on the other hand, similar systemic disease with Neisseria meningitidis virtually always is associated with the characteristic petechial exanthem. Of the other bacterial agents listed in Table 58.3 , exanthem is most important in Neisseria gonorrhoeae, Salmonella typhi, Streptobacillus moniliformis, Spirillum minus, Pseudomonas aeruginosa, and Treponema pallidum .
| EXANTHEM | ||||
|---|---|---|---|---|
| Agent | Disease or Syndrome | Clinical Characteristics | Lesions | Distribution |
| Gram-Positive Cocci | ||||
| Staphylococcus aureus, exfoliative toxin-producing, mainly phage group 2 | Bullous impetigoScalded skin syndrome Toxic epidermal necrolysis (Ritter disease in infants <4 months; Lyell syndrome in older children) Staphylococcal scarlet fever or staphylococcal scarlatiniform eruption | Usually occurs in neonates May be epidemic Usually occurs in infants and children 1 month–5 years of age Mucopurulent nasal and eye discharge Fever Fever and staphylococcal infection in throat but no evidence of pharyngitis | Rapid progression from vesicles to bullous lesions Scarlatiniform eruption with exfoliation Nikolsky sign present Crusty appearance around eyes and under nose Scarlet fever–like rash with desquamation Pastia lines present | Most common in diaper areaGeneralized Most marked on trunkGeneralized |
| Staphylococcus aureus , non–exfoliative toxin producing | Septicemic disease | Severe septicemia with osteomyelitis, arthritis, endocarditis, or pneumonia | Diffuse, erythematous, confluent, and macular rash (flush) With endocarditis, may have petechiae and splinter hemorrhages, Osler nodes, Janeway spots | Trunk and proximal end of extremities |
| Staphylococcus aureus, toxin-1 (TSST-1) producing | Toxic shock syndrome | Fever, intense myalgias, vomiting, and diarrhea Mental confusion and hypotension | Erythematous, deep red (sunburn-like) rash Desquamation occurs | Generalized |
| Staphylococcus aureus, non–exfoliative toxin producing | Folliculitis, furuncles, or carbuncles | See Chapter 60A , “Bacterial Skin Infections” | ||
| Streptococcus pyogenes | Scarlet fever | Fever, pharyngitis, and cervical lymphadenitis Rash onset within 2 days of first symptoms Incubation period 3–4 days | Diffuse erythematous and fine maculopapular (looks and feels like red sandpaper) Rash darker in skin folds (Pastia lines) Desquamation occurs | Circumoral pallor Generalized rash, with trunk and proximal end of extremities being most involved |
| Erysipelas | Fever, headache, and vomiting Localized infection | Circumscribed area that is raised and erythematous Advancing edge is irregular | Anywhere | |
| Impetigo | Localized superficial pyoderma See Chapter 60A , “Bacterial Skin Infections” | Discrete and coalescent lesions of a vesicular nature Quickly becomes more pustular and then crusts over with a yellowish brown appearance | Forearms, legs, and face | |
| Septicemia | Fever and systemic foci of infection | Petechiae | Diffuse | |
| Miscellaneous skin manifestations of S. pyogenes infections | Erythema multiforme, erythema nodosum, and erythema marginatum | |||
| Streptococcus pneumoniae | Septicemia | Fever | Petechiae | Diffuse |
| Enterococcal and viridans group streptococci | Endocarditis | Endocarditis | Petechiae, splinter hemorrhages, Osier nodes, and Janeway spots | |
| Gram-negative cocci | ||||
| Neisseria gonorrhoeae | Gonococcemia | Fever and polyarthralgias | Papular, petechial purpuric, pustular, or necrotic lesions | Most common on extremities Extensor surfaces over joints |
| Neisseria meningitidis | Meningococcemia | Fever and pharyngitis Sudden onset of rash | Characteristic rash is petechial or purpuric Early lesions may be erythematous maculopapular, or urticarial | Generalized |
| Moraxella catarrhalis | Bacteremia | Fever and pharyngitis | Maculopapular and petechial | Generalized |
| Gram-positive Bacilli | ||||
| Bacillus anthracis | Anthrax | Fever, headache, malaise, and joint pain | Initially, macular, pruritic lesion Later, a papule forms and then vesiculation Vesicles last 2–6 days, and then eschar forms | Usually, single lesion initially at point of exposure, secondary lesions in area develop later |
| Listeria monocytogenes | Listeriosis | Neonatal meningitis with hepatosplenomegaly | Maculopapular, discrete lesions Pustules | Trunk and legs |
| Erysipelothrix rhusiopathiae | Crab or fishnet dermatitis | Fever and local pain | Erysipeloid lesion (violet or red) | Hands |
| Corynebacterium diphtheriae | Cutaneous diphtheria | Secondary infection in cutaneous wounds | Impetigo- or ecthyma-like Rarely, erythema multiforme | Exposed surfaces |
| Arcanobacterium hemolyticum | Scarlet fever–like illness | Fever and pharyngitis | Scarlet fever–like rash Occasionally, rubelliform | Generalized rash with peripheral predominance |
| Enteric Gram-Negative Bacilli | ||||
| Salmonella typhi | Typhoid fever | Malaise, headache, and marked fever Rash onset 10 days after onset of fever | Rose spots, 2- to 4-mm macular lesions | Discrete lesions on abdomen |
| Other Salmonella spp. | Septicemic salmonellosis | Similar to mild typhoid fever | Similar to typhoid fever | Similar to typhoid fever |
| Shigella sonnei | Shigellosis | Diarrhea | Urticaria | Diffuse |
| Campylobacter spp. | Gastroenteritis | Skin pustules and erythema nodosum | Lower part of legs | |
| Other Gram-Negative Bacilli | ||||
| Francisella tularensis | Tularemia | Chills, fever, headache, and localized lymphadenopathy | Initial papule that later ulcerates | Site of inoculation |
| Haemophilus ducreyi | Chancroid | Local pain and tenderness | Pustular lesions that ulcerate | External genitalia |
| Haemophilus influenzae | Septicemia | Fever | Petechiae | Diffuse |
| Reddish purple cellulitis | Cellulitis mainly on cheeks and extremities | |||
| Streptobacillus moniliformis | Rat-bite fever | Fever, chills, malaise, headache, and polyarthritis | Erythematous, maculopapular rash that may become petechial | Most prominent on extremities, including palms and soles |
| Yersinia pestis | Septicemic plague | Sudden onset of fever | Initial generalized erythema followed by petechiae and purpura | Generalized |
| Yersinia pseudotuberculosis | Mesenteric lymphadenitis | Erythema nodosum and scarlatiniform eruption | Lower part of legs and generalized | |
| Yersinia enterocolitica | Yersiniosis | Enterocolitis | Erythema nodosum and urticaria | Lower part of legs and generalized |
| Bartonella bacilliformis | Bartonellosis, Carrión disease, or Oroya fever | Initially intermittent fever, malaise, and myalgias 30–60 days after initial fever, exanthem appears | Erythematous maculopapular Later recurrent nodules | Face and extensor surface of extremities |
| Bartonella quintana | Trench fever | Usually mild fever, headache, chills, and tibial bone pain | Macular rash | Mainly on trunk |
| Calymmatobacterium granulomatis | Granuloma inguinale | See Calymmatobacterium granulomatis ( Chapter 130 ) | Nodular, ulcerovegetative, hypertrophic, or cicatricial lesions | Genitals |
| Pseudomonas aeruginosa | Ecthyma gangrenosa | Septicemia (usually in immunocompromised patients) | Initially vesicular and then hemorrhagic Become ulcerated with central black necrotic eschar | Anywhere |
| Pseudomonas folliculitis (health spa dermatitis) | Headache, malaise, and fatigue | Papular and pustular | Generalized | |
| Burkholderia mallei | Glanders, melioidosis | Fever, malaise, chills, arthralgia, and muscle pains | Nodule or ulcer at site of inoculation and then widespread papules, bullae, and pustules | Generalized |
| Brucella spp. | Brucellosis | Acute or subacute febrile illness Erythematous and maculopapular | Exanthem in 8% of urticaria, maculopapular cases Occasionally vesicles | Generalized |
| Legionella pneumophila | Legionnaires’ disease | Severe pneumonia | Maculopapular | Anterior of trunk |
| Bartonella henselae | Cat-scratch fever | Subacute regional lymphadenitis | Erythematous maculopapular, morbilliform, petechial, erythema nodosum, erythema multiforme, and erythema marginatum May be pruritic | Generalized |
| Acid-fast Bacilli | ||||
| Mycobacterium tuberculosis | Lupus vulgaris | Usually associated with other manifestations of tuberculosis | Reddish brown nodular or scaling lesions | Mainly on face and neck |
| Papulonecrotic tuberculids | Associated with disseminated tuberculosis | Initially vesicular Become pustules, umbilical, and ulcerated and then form scabs and leave scars | Single or multiple lesions anywhere | |
| Atypical Mycobacteria | Granulomatous and ulcerative lesions at site of superficial injury | Usually on hands | ||
| Mycobacterium leprae | Erythema nodosum leprosum | General findings of lepromatous leprosy | Erythematous nodular lesions | Disseminated |
| Most prominent on face and extremities | ||||
| Spirochetes | ||||
| Treponema pallidum | Primary syphilis | Chancre | Large ulcers with indurated edges | Genitals |
| Secondary syphilis | Erythematous maculopapules that frequently are scaly (psoriasiform) | Generalized, including palms and soles | ||
| Treponema pertenue | Yaws | Papular lesions at sites of inoculations | Anywhere | |
| Lesions ulcerate, leaving a wart-like appearance | ||||
| Borrelia burgdorferi | Lyme disease (erythema chronicum migrans) | Skin, cardiac, neurologic, and joint abnormalities | Expanding erythematous, annular lesions | Thighs, buttocks, or axillae |
| Treponema carateum | Pinta | Initially, erythematous, papular lesions; increase in size during 1-month period and become scaly | Exposed surfaces of body | |
| Spirillum minus | Rat-bite fever | Fever and chills | Discrete, macular rash | Trunk and extremities, including palms and soles |
| Leptospira spp. | Leptospirosis | Fever, conjunctivitis, and anorexia | Erythematous maculopapular rash | Mainly on trunk |
| Rash rarely noted | ||||
| Borrelia spp. | Relapsing fever | Relapsing fever, headache, myalgia, and photophobia | Morbilliform and petechial Erythema multiforme | Generalized |
Fungal, protozoan, and metazoan agents associated with cutaneous manifestations in humans are listed in Tables 58.4, 58.5, and 58.6 , respectively. These agents and their diseases, discussed more completely in other chapters, are included here for completeness of the differential diagnosis.
| EXANTHEM | ||||
|---|---|---|---|---|
| Agent | Disease or Syndrome | Clinical Characteristics | Lesions | Distribution |
| Dermatophytic fungi | Tinea capitis, tinea cruris, tinea pedis, or tinea circinata | Localized, brownish, maculopapular lesions that are scaly | ||
| Erythema nodosum | ||||
| Candida albicans | Congenital cutaneous candidiasis | Congenital infection | Discrete vesicular lesions | Generalized |
| Chronic mucocutaneous candidiasis | Immunodeficiency disease | Confluent, erythematous, and exudative lesions | Generalized, including scalp | |
| Acquired candidiasis | Confluent, fiery red lesions | Most common in diaper area | ||
| Candida spp. | Systemic candidiasis | Severe opportunistic infection | Erythematous nodular lesions | Generalized |
| Histoplasma capsulatum | Histoplasmosis | Primary respiratory infection | Erythema nodosum, erythema multiforme, and erythematous maculopapular | |
| Cryptococcus neoformans | Cryptococcosis | Primary respiratory infection | Erythema nodosum and acneiform eruptions | |
| Coccidioides immitis | Coccidioidomycosis | Primary respiratory infection | Initially, erythematous, maculopapular rash Later, erythema multiforme and erythema nodosum | Generalized maculopapular rash |
| Sporotrichum schenckii | Sporotrichosis | Cutaneous inoculation | Nodular lesions that ulcerate | Usually, hands, arms, and legs |
| Blastomyces dermatitidis | Blastomycosis | Primary respiratory infection | Nodular lesions that ulcerate Erythema nodosum | |
| Scedosporium spp. | No specific syndrome | Severe opportunistic infection | Nodular or necrotic skin lesions | Generalized |
| Fusarium spp. | No specific syndrome | Severe opportunistic infection | Nodular skin lesions, abscesses | Generalized |
| Aspergillus spp. | No specific syndrome | Severe opportunistic infection | Nodular and purpuric lesions | Generalized |
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