Skip to main content
Open Access Publications from the University of California

Dermatology Online Journal

Dermatology Online Journal bannerUC Davis

Viral exanthems

Main Content

Viral exanthems
Lycia A Scott MD, and Mary Seabury Stone MD
Dermatology Online Journal 9 (3): 4

Department of Dermatology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.


Viral exanthems are mostly associated with self-limited diseases. However, in some cases diagnosis of an exanthem may be crucial to patients and their contacts. Certain exanthems have fairly characteristic morphology, but in many cases an accurate diagnosis cannot be made on the basis of morphology alone. Historical factors may be helpful when evaluating these patients, specifically their disease contacts, immunization record, previous exanthematous illnesses, and associated prodromal symptoms. Some illnesses are seasonal and this knowledge may be useful. This manuscript reviews a number of common childhood exanthems. We included the most common viral exanthems encountered by primary-care physicians and dermatologists.


Goodyear et al. performed a study of 100 children in 1991 with acute febrile illness and rash. Infectious agents were identified in 65 patients, with 72 percent of cases caused by viruses and 20 percent by bacteria. Their findings suggest that most childhood exanthems, associated with fever, are viral in origin.[1] Our intention is to help the clinician elucidate the etiology for a given rash using such clues as prodrome, distribution, and evolution of the lesions. In particular, a description of the rash morphology, systemic symptoms and appropriate treatment recommendations will be discussed. For completeness, a synopsis of pertinent related literature is included. In order to aid in the ease of reading and navigating this manuscript, topics have been organized alphabetically.

Eruptive pseudoangiomatosis

Figure 1

In 1969, Cherry et al. reported a hemangioma-like exanthem in four children aged 8-11 months associated with echovirus infection.[2] They described small erythematous papules with central pinpoint vascular supply and surrounding avascular halo. Direct pressure resulted in complete blanching, and lesions were transient. They hypothesized these lesions were either a direct effect of viral infection on endothelial cells causing capillary dilatation, or antigen-antibody complexes at the vascular site.[2]

In 1993, Prose et al. described three children with bright red papules occurring in association with upper respiratory symptoms consistent with a systemic viral infection; however no organism was isolated.[3] Two 6-month-old children and one 6-year-old child were examined. All had 1-4 mm bright-red papules that blanched completely. All resolved in 7-10 days. Skin biopsy obtained from the 6-year-old showed several dilated capillaries with plump endothelial cells without vascular proliferation or inflammatory infiltrate. They proposed the name eruptive pseudoangiomatosis.[3]

In 1994, two additional cases were reported in siblings with similar skin changes and episodes of fever with diarrhea.[4] The authors proposed a transmissible vector such as a virus as the causative agent, but they were unaware of the Cherry article and did not test for echovirus.

Three additional cases were described in the British literature in 2000, with some peculiar features, none revealing evidence of echovirus infection.[5] The first patient had eruption of lesions when an acute lymphocytic leukemia began. The second patient had no prodromal symptoms. In the third patient, there was an increase in lymphocytes when lesions first appeared. Bacterial cultures were negative. This same patient had recurrent eruption over 3 years, always associated with fever; there was no elevation in lymphocytes with subsequent flares. This pattern had not been previously noted with eruptive pseudoangiomatosis. The serologic tests for Epstein-Barr virus, cytomegalovirus, Coxsackie virus, parvovirus B19, enterovirus, echovirus, and adenovirus were all negative.[5]

In 2000, Guillot and Dandurand reported eruptive pseudoangiomatosis for the first time arising in adulthood.[6] They performed a retrospective study over 10 years, noting eight women and one man with an eruption very similar to those previously reported in children. Histologic findings in the four patients who were biopsied showed findings identical to the biopsy in the Prose et al. report. A few differences were noted clinically, including that fact that not all adults had prodromal symptoms and the duration of the disease was longer for the adults. Onset occurred during hospitalization for treatment of cancer or asthma in four of the nine patients. In the five remaining patients, two were hospitalized in a retirement home, and one was a nurse in a psychiatric hospital. The authors proposed that association with a health-care setting suggested an infectious cause of the eruption despite negative serologic testing.[6]

Ilona Frieden also discussed this possibility in a review, in which she noted reports of bacillary angiomatosis secondary to Rochalimaea infections and in which she finds that recent reports of epidemic Kaposi's sarcoma caused by HHV-8 emphasize that vascular eruptions can be caused by infectious agents.[7]

Treatment of eruptive pseudoangiomatosis is supportive and the disease is self-limited.

Erythema infectiosum and parvovirus B19

Figure 2Figure 3

Figure 4

A common characteristic childhood exanthem first described in 1889, erythema infectiosum was termed fifth disease because of its position in the numerical classification of classic childhood exanthems (following measles, scarlet fever, rubella, and Dukes disease, which is no longer considered a distinct disease).[8] Erythema infectiosum is caused by an acute parvovirus B19 infection. Parvovirus is a single-stranded DNA unenveloped virus, with a tropism for erythroid progenitor cells.

Erythema infectiosum has a worldwide distribution, with school outbreaks in late winter and early spring.[9] It affects primarily the 4-10-year age group, with transmission via respiratory droplets.[10] The incubation period, defined by days prior to appearance of rash, ranges from 4 to 15 days.[8] Occasionally, mild prodromal symptoms precede the rash; these include low-grade fever, headache, pharyngitis, malaise, myalgias, nausea, diarrhea, and joint pain. The infectious period spans from 7 days preeruption until the first appearance of rash in normal individuals.[11] However, in patients with aplastic crises, they are potentially contagious for an extended period of time; infectivity may continue for up to a week or more after the rash appears.[12]

Erythema infectiosum is characterized by confluent erythematous, edematous patches or plaques on the cheeks, with sparing of the nasal bridge and periorbital regions. These so-called slapped cheeks fade over 1-4 days. The rash spreads to the trunk and extensor extremities, which undergo patchy clearing resulting in a lacy reticular pattern and may be pruritic.[8, 12] This eruption lasts 5-9 days but can recur for weeks to months with triggers such as sunlight, exercise, temperature change, bathing, and emotional stress. [11]

An enanthem may be present consisting of erythema of the tongue and pharynx, often with red macules on the buccal mucosa and palate. Arthralgia or arthritis are seen in 10 percent of affected children, and typically involve large joints for a brief duration.[8]

In adults, primary infection results in more severe constitutional symptoms. Fever, adenopathy, and arthritis, particularly in women, without a rash, is the usual course.[12, 13] If an exanthem is present in adults it is usually a macular, lacelike eruption beginning on the extremities and often progressing caudally.[12]

In parvovirus B19 infection severe outcomes may occur in three groups of patients. These include the immunocompromised, the fetus, and patients with hemoglobinopathies. In the patients with chronic hemolytic anemias, a transient aplastic crisis manifested by anemia, reticulocytopenia, and red-blood-cell aplasia may result. Aplastic crisis may be seen in hereditary spherocytosis, sickle-cell disease, G6PD deficiency, pyruvate-kinase deficiency, iron deficiency, and the thalassemias.[8] Aplasia is self-limited and responds well to transfusions. Not all individuals have a clinically evident rash, and they therefore serve as source for an outbreak.[14] In normal individuals, parvovirus B19 infections are inconsequential because circulating erythrocytes have a long life-span.

In the immunocompromised patients, such as those with HIV, congenital immunodeficiencies, acute leukemia, organ transplants, and lupus erythematosus, or in infants less than 1-year-old, parvovirus B19 can cause a serious prolonged chronic anemia owing to persistent lysis of RBC precursors. Administration of IVIG, which contains pooled, neutralizing anti-B19 antibody, has been used successfully in immunodeficient patients.[12, 14]

During pregnancy, parvovirus B19 infection may result in vertical transmission to the fetus, causing infection of erythroid precursors and extensive hemolysis, leading to severe anemia, tissue hypoxia, high-output heart failure, and generalized edema (hydrops fetalis). Most reported fetal losses secondary to parvovirus B19 have occurred in the first trimester of pregnancy.[10] Immunity is conferred after infection, and 50 percent of women of child-bearing age are seropositive(IgG) with absence of IgM, indicating prior infection.[15] The vertical transmission rate, in infants exposed to infected mothers during gestation (confirmed by IgG positivity in children at 1 year) is reported as 16 percent if exposed during the first 20 weeks and 35 percent after 20 weeks gestation. The risk of developing hydrops fetalis from hemolytic anemia is 10 percent and the rate decreases as pregnancy progresses.[12] Levy et al. reviewed the literature and found rates of fetal loss, out of 334 cases, to be 6.5 percent with an additional 0.6 percent with non-fatal hydrops fetalis.[10] Newer reports estimate the incidence, up to 20 weeks, to be close to 9 percent for fetal loss and 3 percent for hydrops fetalis after the mother is infected.[15]

Other severe sequelae may rarely occur. In 1997, a 9-month-old boy developed encephalopathy associated with the onset of erythema infectiosum, resulting in permanent neurologic sequelae.[16] More recently, a 2-year-old boy developed acute cerebellar ataxia, thought to occur as the result of transient vascular reaction in the cerebellum during parvovirus B19 infection.[17]

Treatment of Parvovirus B19 infection is symptomatic. Patients with chronic hemolytic anemias who develop transient aplastic crisis (pallor, weakness and lethargy) need to be treated for symptoms of anemia and may require blood transfusion.[12, 14] Pregnant women, with signs or symptoms suggestive of B19 infection or known recent exposure to infected contacts, should have serum B19 IgM and IgG titers drawn.[11] If maternal infection is supported, by positive IgM and IgG levels then serial fetal ultrasounds should be performed to evaluate for changes of hydrops fetalis, and interpreted by an experienced physician.[10] These patients should also be referred to a tertiary care center for cordocentesis and possible fetal blood transfusion, if indicated.[10, 12, 15]

Because patients with aplastic crises are contagious for extended periods of time and immunosuppressed patients may have chronic parvoviral infection, droplet precautions are recommended when caring for those patients.[12] Some patients may have only transient aplasia or erythrocyte crisis and in these individuals droplet precautions should be continued for 7 days. Pregnant health-care workers should be advised of the risks of participating in the care of these patients as well as educated about preventive measures, which include nonparticipation in care of immunosuppressed patients or those with aplasia.[12] However, routine exclusion of pregnant women from the workplace is unlikely to be effective because the virus is transmitted before the rash appears in routine cases.[11, 12] This philosophy also applies to allowing children attend school who have uncomplicated erythema infectiosum, because these children are not contagious. Transmission of parvovirus, like other infectious agents, is also probably lessened by routine hygiene practices.[12]

Gianotti-Crosti syndrome (papular acrodermatitis of childhood)

Figure 5Figure 6

This eruption was described in 1955 by Gianotti and again by Crosti & Gianotti in 1957 and termed papular acrodermatitis of childhood. Initially, most reported patients, from Italy and Japan, had an associated hepatitis B infection. However, Gianotti also described a nearly identical rash without associated Hepatitis B virus infection, which he termed papulovesicular acrolocated syndrome.[18, 19, 20]

Historically, papular acrodermatitis of childhood and papulovesicular acrolocated syndrome were characterized, respectively, by the presence or absence of hepatitis B infection, a distinction that has been more recently abandoned.[18] As stated above, the vast majority of hepatitis-associated cases are in the Mediterranean and Japanese literature, where there is a high prevalence of hepatitis B infection. Series of Gianotti-Crosti syndrome (GCS) cases in North America and Western Europe, where hepatitis B infection is not as common, have demonstrated the presence of other viral etiologies, such as EBV, in addition to hepatitis B.[18, 19] In 1992, a retrospective review of 308 cases by Caputo et al. in Italy found less than 25 percent of patients to have hepatitis B infection. Furthermore, they were unable to distinguish any difference in the exanthem between patients with and without hepatitis.[20] Other more commonly reported associations include CMV, coxsackie A16, parainfluenza, MMR, influenza, diphtheria, pertussis, polio, and BCG vaccinations.[21] A recent report by Andiran et al. reported a combination measles and hepatitis B vaccine as a new cause of GCS.[22]

The majority of patients with GCS are 1-6 years old with a range from 3 months to 15 years. Most patients will have a prodrome consisting of fever and upper respiratory symptoms. The exanthem consists of discrete, nonpruritic, erythematous, monomorphic papules, and occasionally papulovesicles on the face, buttocks, and extensor surfaces of the extremities. The trunk is spared. Patients may have an associated lymphadenopathy, hepatomegaly, or splenomegaly. The rash usually resolves in 2-3 weeks, although it may last up to 8 weeks.[23]

Treatment is symptomatic. Appropriate evaluation is recommended if hepatitis suggested by history or physical exam.

Hand-foot-mouth disease

Figure 7Figure 8

Figure 9Figure 10

Figure 11

This clinical entity was first reported by Robinson and Rhodes in 1958. They reported an exanthem with associated fever and oral lesions, noted in over 60 persons in June and July 1957 in Toronto, Canada. Coxsackie virus A16 was isolated from two-thirds of 27 stool specimens studied. The next reported epidemic of coxsackie occurred in Birmingham, England, in the summertime of 1960 and was described by Alsop et al. who noted vesicular lesions on the hands and feet with oropharyngeal lesions and who termed the eruption hand foot and mouth disease.[24]

Hand-Foot-Mouth Disease (HFMD) is highly contagious, spread by oral-oral and fecal-oral routes. It typically affects children under 10 years old. Vertical spread from mother to fetus also occurs. In temperate climates, as in the United States, infection is more common during late summer and early fall.[25]

HFMD is caused by enteroviruses, members of the picornavirus group (single-stranded RNA, unenveloped) and is most commonly associated with coxsackie virus A16 or enterovirus 71.[25] Sporadic cases associated with coxsackie A 4-7, A9, A 10, B1-B3, and B5 have also been reported. Infections are usually sporadic but epidemics do regularly occur. Epidemics tend to occur every 3 years in the United States.[25] Initial viral implantation is in the buccal mucosa and ileal mucosa and is followed by spread to regional lymph nodes within 24 hours. Viremia rapidly follows and virus spreads to oral mucosa and skin. By day 7 after infection, serum antibody levels increase, and the virus disappears.[25]

After an incubation period of 3-6 days, a brief 12-36 hour prodrome of low-grade fever, malaise, cough, anorexia, abdominal pain, and sore mouth occurs. Patients may present with either enanthem or exanthem but most manifest both. Painful ulcerative lesions occur anywhere in the oral cavity, but are most commonly found on the hard palate, tongue, and buccal mucosa. The exanthem begins as 2-8-mm erythematous macules and papules, which progress through a short vesicular stage to form a yellow-gray ulcer with an erythematous halo. Lesions may coalesce, the tongue may become red and edematous, and pain may interfere with oral intake. Oral lesions resolve without treatment in 5-7 days. The exanthem, characterized by 2-3-mm erythematous macules or papules with a central gray vesicle, usually appears shortly after oral lesions, with the hands more commonly involved than the feet. The sides of the fingers and dorsal surfaces more often are involved than palms and soles. Lesions appear elliptical, with the long axis running parallel to skin lines, and may be asymptomatic or painful. They crust and gradually disappear over 5-10 days without scarring.[25]

Although most cases resolve with no long-term complications, first trimester infection may lead to spontaneous abortion or intrauterine growth retardation.[25] Other complications have been reported including myocarditis, meningoencephalitis, pulmonary edema, and even death.[25]

Recent epidemics of HFMD with enterovirus 71 have been associated with neurologic complications. In September 1999, Huang et al. from Taiwan identified 41 children with confirmed enterovirus 71 infection, 68 percent diagnosed with HFMD and 15 percent with Herpangina. Three neurologic syndromes were identified: acute flaccid paralysis (10%), aseptic meningitis (7%), and brain-stem encephalitis or rhomboencephalitis (90%). Rhomboencephalitis, with a 14 percent fatality rate, most commonly presented with myoclonic jerks; MRI showed brain-stem involvement.[26] Another report from Taiwan published in the Journal of Clinical Virology in 2000, noted an outbreak of enterovirus in 1998. From April through December, 405 children were hospitalized with 78 deaths. Enterovirus 71 was isolated in 119 cases, with resultant diseases of HFMD in 54, HFMD with CNS involvement in 37, herpangina in 12, aseptic meningitis in three, encephalitis meningoencephalitis in ten and acute flaccid paralysis in three. Nine fatal cases were complicated by neurogenic pulmonary edema. The most critical early sign of Enterovirus 71 infection with CNS involvement was myoclonus with sleep disturbance.[27]

Treatment of HFMD is symptomatic, aimed at providing relief of painful oral lesions with agents such as viscous lidocaine, dyclonine solution, diphenhydramine, magnesium hydroxide and sucralfate.

An open, uncontrolled study in 1996 by Shelly et al. studied 12 children and one adult with HFMD and treated these patients with oral acyclovir within 1-2 days after onset of mucosal and cutaneous lesions. They observed symptomatic relief and involution of lesions within 24 hours. The authors proposed that the efficacy was due to an antiviral enhancement of the patients' own interferon, because coxsackie A16 lacks thymidine kinase (the enzyme inactivated by acyclovir).[28]


Herpangina was described as a specific entity by Zahorsky in 1920. Reports of outbreaks in nursery schools and summer camps followed in 1939 and 1949. The first viral implication occurred later when Cole et al. isolated group A coxsackie virus from stool samples and throat washings in herpangina patients published in 1951.[29] Herpangina is typically caused by coxsackievirus group A1 to 6, 8, 10, and 22. Other causes include coxsackie group B (strains 1-4), echoviruses, and other enteroviruses.[30]

Herpangina affects any age group but is seen primarily in infants and young children below the age 5. In temperate climates, infections occur in late summer or early fall.[29] A febrile illness without oropharyngeal lesions or a subclinical infection may be seen in the siblings of a patient with herpangina.[29, 31]

The incubation period ranges from 1 to 10 days, usually lasting 4 days. This period is followed by the sudden onset of fever with malaise, headache, and neck or back pain. The enanthem consists of 1-2-mm gray-white papulovesicular lesions that progress to ulcers surrounded by an erythematous rim and diffuse pharyngeal hyperemia. Lesions are distributed on the anterior tonsillar pillars, soft palate, uvula, and tonsils and last 4-6 days. Affected patients often complain of anorexia, dysphagia, and sore throat.[31] No associated exanthem is typically seen. Rarely, neurologic complaints may ensue.[26] The disease is self-limited with high fever rarely lasting more than 4 days and oral lesions rarely more than 7 days.[31] Treatment is symptomatic.

Measles (rubeola)

Figure 12Figure 13

Figure 14

There are descriptions of measles dating back to the tenth century. During the seventeenth century measles was delineated from other diseases by clinical and epidemiologic observations by scientists such as Thomas Sydenham. In 1954 Enders and Peebles isolated the measles virus in tissue culture, and in 1960, they successfully attenuated the measles virus.[31] Measles is caused by paramyxovirus, a single-stranded RNA, enveloped virus. In 1963, the measles vaccine was introduced. The initial recommendation for a single dose of vaccine at 9 months was changed to 12 months in 1965 and to 15 months in 1976. Vaccination resulted in a dramatic reduction in the number of cases, to a low in 1983 of 1,497 cases.[32]

In the mid- to late 1980s a resurgence of measles occurred, as a result of the declining immunization rates in poor urban children and the insufficiency of a single dose of vaccine to provide long-term immunity.[32] The incidence of measles was again decreased because of intensive public-health efforts and increased vaccination coverage. In 2000, a total of 86 confirmed measles cases were reported to the CDC. This represented a record low and a decrease from 100 cases reported each year for the previous 2 years.[33] Currently, the majority of cases in urban centers occur in infants and toddlers; in rural, less crowded areas the highest incidence is in the 5- to 10-year-old age range.[31]

Measles mainly occurs in the winter and spring, with peak incidence in March and April.[31] The mechanism of infection is droplet spread of secretions. The primary site of infection is the respiratory epithelium of the nasopharynx.

The asymptomatic, incubation period is 10-11 days, with a prodromal phase lasting 1-7 days. Associated fever approaches 40-40.3° C at the peak of the eruption and then falls quickly. Other symptoms include severe, common-cold-like symptoms (coryza) and conjunctivitis which extends to the lid margin, resulting in a red-rimmed eye. There is also a brassy, barking cough that persists for 1 week after the coryza resolves.[31]

The rash is composed of erythematous macules and papules appearing behind the ears and at the anterior hairline, coalescing, spreading over the neck and trunk distally, and finally affecting the upper and lower extremities including the hands and feet.[31] Measles spreads more slowly than does rubella, with the entire body involved by day 3. The rash fades in order of appearance, and as it disappears, it becomes nonblanching and brownish-yellow as the result of capillary hemorrhage. Differing amounts of fine branny desquamation may be seen.

Typically, an enanthem is also present. Pinpoint elevations begin on the soft palate and coalesce as the entire pharynx becomes red, lasting 6-7 days. On the tonsils Herman spots occur, described as bluish-gray areas. However, the pathognomonic lesions are Koplik spots, which are punctate blue-white lesions surrounded by an erythematous ring (so-called grains of sand on a red background) on the buccal mucosa, opposite the second molars. Koplik spots appear 1-2 days prior to the onset of the exanthem and remain for 2-3 days. Similar lesions are occasionally seen on the conjunctivae at the medial canthus and in the large intestines.[31]

Atypical measles occurs in patients who received killed viral vaccine (used in United States from 1963 to 1967) and are subsequently infected with natural measles. High fever, myalgias, cough, headache, abdominal pain, edema of extremities, pleural effusion, pneumonia, and hilar adenopathy occur. Lesions are erythematous maculopapules, which progress to petechiae, vesicles, and palpable purpura, beginning on hands and feet and spreading centripetally. The major differential diagnosis is Rocky Mountain spotted fever.[31]

Modified measles occurs in a partially immune host secondary to a prior infection, persistent maternal antibodies, or immunization. Clinically, the illness is much milder than ordinary measles. The course is shorter, the exanthem is less confluent, and Koplik spots may be absent.

Complications are more likely to occur in the very young and in the malnourished. Encephalitis occurs in 1 in 800 cases, is unpredictable, and most recover fully. Death and brain damage occur only in a small minority. Thrombocytopenia and resultant purpura or lymphopenia may occur. Bacterial superinfections, including otitis media or pneumonia, are heralded by a second fever spike. Subacute sclerosing panencephalitis (SSPE) may be a late developing complication and occurs in 1 in 100,000 cases. It is a delayed, degenerative disorder of the nervous system resulting in mental and motor deterioration months or years after uneventful acute measles. Personality changes, myoclonic seizures, coma, and death characterize SSPE. Measles viral antigen has been demonstrated in brain tissue, with elevated serum and CSF antibody titers and elevated total CSF IgG. Infection in pregnant patients has been associated with fetal death.[31]

Therapy for measles is supportive and includes rest, hydration, nutrition, vaporizer, antitussives, and respiratory isolation. Ribavarin intravenously or via aerosol has been used for severely affected patients or those who are immunocompromised, but there are no current recommendations regarding antiviral therapy.[34]

In 1987, the WHO and UNICEF issued a joint statement recommending administration of vitamin A to all children diagnosed with measles in communities where vitamin A deficiency is a recognized problem.[35] Vitamin A had been shown to decrease morbidity in hospitalized patients. Furthermore, Hussey and Klein documented low serum retinol levels during the acute phase of measles in a population without endemic vitamin A deficiency. They found low retinal levels to be associated with more severe measles, assessed by higher fever, longer febrile episodes, increased rates of hospitalizations, and lower antibody titers. Treatment with vitamin A, in the study by Hussy and Klein, decreased morbidity and mortality. Therefore, their recommendation is that all children with severe measles should be given vitamin A supplements, regardless of nutritional state.[34] Immune serum globulin (ISG) may prevent or possibly modify disease if given within 6 days of exposure and is recommended in exposed infants who are too young for vaccination or immunocompromised children and adults.[31]

People are considered susceptible to measles unless they have history of physician-diagnosed measles, serologic evidence of immunity, or documented vaccination. The current recommendation is for administration of live, attenuated vaccine in a two-dose schedule. The first MMR dose is recommended at 12-15 months followed by second dose at 4-6 years. HIV infection is not a contraindication to measles vaccine.[31]

Papular-purpuric gloves and socks syndrome

Figure 15

In 1990 Harms et al. described five patients with this acute self-limited eruption.[36] More than half of the reported cases of papular-purpuric gloves and socks syndrome (PPGSS) are linked to parvovirus B19, first noted in serology reported by Bagot and Revuz published in 1991.[37] This finding was confirmed in 1992 by Halasz et al. with antibody titers and in 1997 by Smith et al.[38,39] Other reported etiologies include measles virus, EBV, CMV, HHV6, coxsackie B6, and hepatitis B.[40-46] Parvovirus B19, however, is the only etiologic agent that has been found to be present in peripheral blood and skin biopsy specimens by PCR.[47]

Recently, Van Rooijen et al. from Germany reported a classic case of PPGSS that developed after taking trimethoprim-sulfamethoxazole. The patient again developed identical symptoms after rechallenge with the drug. This suggests that PPGSS is a manifestation of an underlying immunologic mechanism that may be induced by viral or drug-related antigens.[48]

PPGSS occurs most commonly in young adults, primarily during the spring and summer.

The incubation period is about 10 days. The rash may be followed in 2-4 days by myalgias, arthralgias, lymphoadenopathy, anorexia, and fatigue. Leukopenia or thrombocytopenia may be seen. The patient is overall nontoxic appearing. Symmetric erythema and edema of the hands and feet progress to petechial and purpuric macules, papules, and patches that are followed by fine desquamation. There is a characteristic, sharp demarcation at the wrists and ankles. Rarely, the eruption may extend to nonacral sites such as face, buttocks, trunk, groin, and extremities. The eruption may occasionally be painful or pruritic.[39] The majority of patients have an associated polymorphous enanthem, including diffuse hyperemia, aphthae, petechiae, and erosions on palate, pharynx, tongue, and possibly inner lips. Grilli et al. described one case with accompanying vulvar edema, erythema, dysuria, and unilateral petechial rash on the breast with confirmed acute parvovirus B19 infection.[48] PPGSS spontaneously resolves in 1-2 weeks without any known late sequela.[39]

Histopathologic examination has not been done on the majority of reported patients, but reported biopsies have shown a lymphocytic, perivascular infiltrate in the papillary dermis with extravasated RBCs. No vasculitis is seen. By immunofluorescence, using antibody to parvovirus B19, virus is detected in the endothelial cells of dermal vessel walls, the sweat glands, and epidermal ductal structures, suggesting a vascular reaction to a viral antigenic stimulus.[39]

Treatment is symptomatic with moisturizers and antihistamines as needed.

PPGSS is unlike erythema infectiosum where skin signs develop after clearance of viremia and in the presence of rising antibody titers. Patients with slapped cheeks are therefore considered noninfectious. In PPGSS, the immune response against parvovirus B19 occurs later, after the onset of the skin eruption. Therefore, patients with clinical signs of purpuric gloves and socks secondary to parvovirus B19 are potentially infectious. This fact has important implications regarding contact with seronegative pregnant patients and immunocompromised individuals and those with chronic hemolytic anemias, because of the same concerns as in fifth disease for aplastic anemias, hydrops fetalis or fetal loss, and a prolonged severe infection.[49,50]

Pityriasis rosea

Figure 16Figure 17

Figure 18

Pityriasis rosea (PR) is an acute self-limited disorder affecting primarily children and young adults. PR exhibits seasonal clustering; a viral trigger has long been suspected. There are many factors that are suggestive of a viral etiology, the case clustering, prodromal features, increased erythrocyte sedimentation rate, and biopsy findings of dyskeratotic cells and multinucleated giant cells in the epidermis. In addition, the induction of a PR-like eruption can be produced by subcutaneous injection of tissue fluid from PR lesions. However, on the basis of the current literature, no conclusive association of a known virus has been established.[51]

In 1997, Drago et al. evaluated HHV-6 and HHV-7 as candidate etiologic agents of PR. They studied skin tissue and blood from 12 patients with acute PR, 12 with other dermatoses (dermatologic controls), and 25 healthy controls. They found HHV-7 in the peripheral blood mononuclear cells of all patients with active or relapsing PR, and 11 out of 25 healthy controls. HHV-7 was also found in all skin and plasma specimens in the patients with PR. None of the dermatologic controls had HHV-7 in skin specimens, and no healthy controls had plasma HHV-7. Detection in PBMC indicates infection but not causality or activity. Viral DNA in body fluids indicates active viral replication in vivo; virus in the plasma therefore represents active infection and supports a causal relationship. Additional supporting evidence for a viral infection are numerous cytopathic changes, including viral footprints such as interferon-α in plasma and a cytopathic effect in cocultured mononuclear cells.[52]

Conversely, in 1999 Kempf et al. performed a retrospective cross-sectional survey of 13 patients with PR and 14 control subjects. Using PCR, they found the HHV-7 DNA prevalence to be slightly lower in the lesional skin of PR patients than controls. They argued that the low detection rate of HHV-7 DNA spoke against a causal role for HHV-7 in PR.[53] A letter to the editor in 2000 proposed that the results found by Drago et al. may have been falsely positive because of PCR contamination.[54] Further, in the 2000 British Journal of Dermatology, Kosuge et al. reported no difference in the prevalence of HHV-6 or HHV-7 in peripheral blood mononuclear cells between 44 patients with PR versus 25 patients with other skin disorders. However, serologically increased HHV-6 and HHV-7 titers were noted in four and seven PR patients, respectively, consistent with active infection. They concluded that HHV-6 and HHV-7 may play a part in some patients with PR, but other causative agents may exist. They noted that differences in the time of collection of tissue samples may explain the different results reported and that many causative agents may cause the same exanthem.[55]

A rebuttal by Drago et al. in 2001 to the British Journal of Dermatology argued that the difficulty with implicating HHVs is due to their ability to establish a state of latent infection and therefore negative test results are of limited utility. They further stated that HHV may be implicated but difficult to prove without evidence of viral replication, which they claimed to have done in 100 percent of their PR cases in 1997.[56]

PR occurs primarily in 15-40-year-olds, especially women, typically in the spring and autumn. The exanthem in PR consists of discrete oval salmon-colored papules and macules that may become confluent. The eruption often begins with a single herald patch, a week or more before the other smaller lesions. Mild constitutional symptoms may precede the herald patch. The oval patches are covered by a finely crinkled, dry epidermis that desquamates leaving a collarette of scale. Lesions spread rapidly and usually disappear spontaneously after 2-6 weeks.[51] The lesions follow Langer's cleavage lines, arranged along their long axis. Chuh has recently argued that rash orientation is inappropriately described with terms such as Christmas-tree pattern, fir-tree pattern, parallel to the ribs, or along skin cleavage lines.[57] Pruritis may be present. An unusual variant, common in children (especially black children) under the age of 5, is papular PR, with the same distribution and a similar course. An inverse variant, involving the axillae and groin also occurs.

In 2000 Sharma et al. reported a double-blind, placebo-controlled clinical study with 90 PR patients over 2 years who were placed in either an erythromycin-treatment group or placebo group.[58] Patients received erythromycin for 14 days. Complete response was observed in 73 percent of the treatment group in 2 weeks versus none in the placebo group.

A follow-up study by Chuh et al. published in the European Journal of Dermatology in 2002 used the success of erythromycin as the basis for a prospective case-control study of 13 patients with PR looking for an infectious etiology. Serology profiles were not diagnostic of an active infection by Chlamydia pneumoniae, C. Trachomatis, Legionella longbeachae, L. micdadei, L. pneumophila or Mycoplasma pneumonia infections. They concluded that anti-inflammatory and immunomodulatory effects might explain the action of erythromycin in PR.[59]

Treatment is generally symptomatic. After the acute inflammatory stage has passed, ultraviolet B may be used to expedite involution of the lesions. Topical steroids, emollients, and antihistamines may be used for the pruritus, which may be intense.[31]

Roseola infantum (exanthem subitum)

Roseola infantum (RI) was described by Zahorsky in 1910 as a febrile exanthem occurring in infants and young adults.[60] This description was followed in 1913 by the definitive description of roseola in JAMA.[61] The earliest published description was likely in 1809 by British dermatologist, Robert Willan. In 1988, Yamanishi et al. isolated HHV-6 from peripheral blood lymphocytes and cord blood, which demonstrated that this virus, a double-stranded DNA B-cell lymphotrophic virus, is the major agent responsible for roseola infantum.[62]

HHV-6 primarily affects children between 6 months and 2 years. Maternal antibodies play a role in preventing infection prior to 6 months of age. By 12 months, two-thirds of children have been infected with HHV-6 with peak antibody levels being reached at 2-3 years. HHV-6 is shed in the saliva. In adults, primary infection with HHV-6 can produce a mononucleosis-like illness; it more rarely causes severe disease, including encephalitis. This same illness can be caused by HHV6 during reactivation, particularly in immunocompromised persons.[63]

The incubation period of HHV-6 is estimated at 5-15 days, followed by abrupt onset of high fever (39-40° C), cervical lymphadenopathy and mild upper respiratory symptoms. The fever lasts 3-5 days, after which there is an abrupt defervescence, coinciding with rapid onset (subitum is latin for suddenly) of a rash within 24-48 hours. The exanthem consists of nonpruritic, rose-pink, 2-3-mm discrete macules and papules that blanch on pressure and are surrounded by white halos. The eruption is first seen on the trunk, then spreads to the neck and extremities. The rash fully evolves in 12 hours and lasts 1-2 days. Palpebral and periorbital edema (Berliner's sign, heavy eyelids, is quite common.[63]

In addition to RI, HHV-6 has been associated with seizures and in some cases it is unclear whether seizures are secondary to fever or to the HHV-6 infection itself.[64] There are also rare reports of hepatitis, pneumonitis, neuropathy, meningoencephalitis, thrombocytopenia, intussusception, and encephalopathy having been observed after classic exanthem subitum.[63] Even though many patients with central nervous system involvement have a normal recovery, chronic neurologic sequelae such as hemiparesis have been reported.[65] It is postulated that active viral replication occurs in the central nervous system, because the virus has been cultured from the cerebral spinal fluid.[66]

A study in 2002 by Hashimoto et al. suggests that thrombocytopenia observed with roseola infantum results from bone-marrow suppression rather than from immune-mediated peripheral consumption.[67] Even though many patients with central nervous system involvement have a normal recovery, chronic neurologic sequelae such as hemiparesis have been reported.[65]

Because most cases are benign and self-limited. Treatment is supportive.[63]

Rubella (German or 3-day measles)

Figure 19Figure 20

A togavirus causes rubella, also known as German measles, which is a single-stranded RNA, enveloped virus. The distribution of the disease is worldwide, and in North America outbreaks tend to occur more frequently in spring.[68]

In the United States today, rubella outbreaks usually involve individuals from foreign countries where rubella vaccinations are not routine. Outbreaks mainly occur in Latin American communities in recent immigrants.[69]

Rubella is thought to be spread by respiratory secretions with an incubation period of 12-23 days. A prodrome occurs 1-5 days prior to the rash with low-grade fever, headache, conjunctivitis, sore throat, rhinitis, cough, and adenopathy. The eruption presents with pink-red macules and papules on the face and spreads caudally over 24 hours. The exanthem begins to fade after 1-2 days in order of appearance and completely disappears in 2-3 days. There is often an enanthem with punctate erythematous spots scattered over the soft palate and uvula, called Forcheimmer sign.[68] Lymphadenopathy is prominent in Rubella, affecting all nodes, especially suboccipital, postauricular, and posterior cervical nodes. Splenomegaly is noted on occasion. Arthritis may occur and is more common in adults, especially women. Arthritis involves both small and large joints with or without swelling and is usually first noted as the rash fades.[68]

Encephalitis occurs in 1 in 6000 cases, is usually mild, and followed by complete recovery. Thrombocytopenia with resultant purpura, epistaxis, gastrointestinal hemorrhage, and hematuria may occur and usually resolves within 1 month. Peripheral neuritis is a rare complication.[31]

In the United States population about 10 percent of women of childbearing age may be susceptible to rubella.[70] The reported rubella and congenital rubella syndrome (CRS) cases are at record low levels. Most infants with CRS are born to mothers born outside the United States[71] In the United States from 1997 through 1999, 83 percent of CRS infants were born to Hispanic mothers and 91 percent born to foreign-born mothers.[69]

Rubella exposure during pregnancy may result in intrauterine infection and subsequent fetal damage. The fetus is most susceptible during the first and second trimesters.[70] Approximately 90 percent of fetuses exposed during the first trimester develop clinical infection but not all develop CRS. Infection early in pregnancy may result in low birth weight, microcephaly, mental retardation, cataracts, nerve deafness, and congenital heart disease (usually patent ductus arteriosus or ventricular septal defect), neonatal purpura, and neurologic defects.

Infection occurring later in pregnancy, after organogenesis, provides a variable clinical picture, which may include hepatitis, splenomegaly, pneumonitis, myocarditis, encephalitis, osteomyelitis, retinopathy, and bone-marrow involvement, leading to so-called blueberry-muffin baby with petechiae and ecchymoses. The blueberry-muffin lesions represent sites of dermal erythropoiesis and are also seen in other congenital TORCH infections such as cytomegalovirus and toxoplasmosis infections.[70]

Rubella virus may be cultured from nasopharynx, urine, CSF and cataract lens. In first month of life 81 percent of CRS patients shed virus, and some become chronic carriers of the virus. Therefore, these patients should not be handled by those caregivers at risk for infection.[70]

Treatment of rubella is supportive.[70] Lifelong immunity usually follows an acute infection. Subclinical reinfection is rare. The live, attenuated vaccine is given as part of the measles, mumps, and rubella (MMR) vaccine in two doses, one at 12-15 months followed by a second dose at 4-6 years. Seroconversion is 95 percent or higher after a single dose. Prenatal screening for susceptibility in mothers is now routine. Immunization was previously not recommended less than 3 months prior to pregnancy. However, recent MMWR indicates that no cases of CRS have been identified among infants born to women who were vaccinated inadvertently within 3 months of pregnancy or early in pregnancy.[72] Therefore, the Advisory Committee on Immunization (ACIP) shortened its recommended period to avoid pregnancy after receipt of rubella-containing vaccine from 3 months to 28 days prior to pregnancy.

A child or adult who is immunized does not shed sufficient virus to infect susceptible individuals in close contact. Immunization of children in a family in which the mother is pregnant is considered safe.[70,72]

Unilateral laterothoracic exanthem (asymmetric periflexural exanthem of childhood)

Figure 21

Brunner et al. described an eruption as lichen miliaris in 1962, which had unilateral, periflexural involvement.[73] In 1992 the term, Unilateral Laterothoracic Exanthem (ULE), was proposed by Bodemer and de Prost, who reported 18 children with a mean age of 23.3 months with a unilateral eruption, either eczematous or scarlatiniform, localized to an axilla.[74] The majority of patients (10 of 18) had fever, sore throat, conjunctivitis, rhinopharyngitis or diarrhea. Serologic testing for virus was negative. An etiology was not established, but a viral cause was suggested. In a recent prospective case series of 67 children, Coustou et al. also found no evidence to support interhuman transmission, nor was a link with pityriasis rosea evident.[75] In 1993, Taieb et al. reported 21 cases with a similar eruption, and, because the eruption did not always remain unilateral and could involve the lower extremities, they suggested the name Asymmetric Periflexural Exanthem of Childhood (APEC).[76]

A large prospective study reported the mean age of those affected with ULE to be 24.3 months, with a 2-to-1 female predominance. The majority of cases (85.4%) occur in winter and spring.[77]

The rash has erythematous macules or papules that form morbilliform, scarlatiniform, or eczematous patterns. The primary lesion is a micropapule with a surrounding pale halo that progresses through an eczematous phase,[50] which begins unilaterally in the axilla or groin, spreads centrifugally, and usually resolves spontaneously by 4 weeks. Both sides of the body are usually ultimately involved, however there is continued unilateral predominance. Sparing of the palms, soles, and mucous membranes is typical. Adenopathy and low-grade fever are present.[50, 75, 77]

In 1999, Coustou et al. reported new clinical variants, including association with fever up to 40 degrees Celsius, and confirmed their previous findings from 1993 (Taieb), of the extended course, up to 60 days, of the eruption. They also confirmed previous clinical observations of atypical features, such as facial involvement and peripheral extension. Skin biopsy specimens obtained had a dermal lymphocytic infiltrate predominantly around sweat glands, with less involvement around blood vessels and hair follicles.[75]

A prospective study in 1996 by McCuaig et al. in Quebec studied 48 children to determine the clinical evolution of ULE, its response to therapy, and histologic features. Thirty children had pruritis and eight showed mild lymphadenopathy. Late desquamation was present in all patients. They also found patients with involvement of the face, genitals, and the hands and feet. Histologic findings also revealed a prominent lymphocytic infiltrate of eccrine glands and ducts.[77]

The origin of this eruption remains unknown, in spite of a continued, active search for an infectious etiology.[77] However, an infectious etiology is suspected because of a seasonal pattern and the presence of prodromal symptoms. The study by Bodemer and de Prost reported negative serologic testing for hepatitis B, EBV, CMV, HIV, coxsackie, parvovirus, mycoplasma, borreliosis, rickettsiae, toxoplasmosis and spiroplasma (which was implicated in earlier reports).[74]

The treatment of ULE is symptomatic, utilizing moisturizers or antihistamines if needed. Topical steroids have been found to be ineffective.[75]

Although viral exanthems are usually associated with benign, self-limited diseases, in some cases correct diagnosis of an exanthem may be required for proper treatment, monitoring, and initiation of preventive measures for contacts. Knowledge of exanthem morphologies and historical data combined with selective laboratory testing should lead to appropriate management of these patients and their families.


1. Goodyear HM, Laidler PW, Price EH, Kenny PA, Harper JI. Acute infectious erythemas in children: a clinico-microbiological study. Br J Dermatol 1991; 124:433-438.

2. Cherry J, Bobinski J, Horvath F, Comerci G. Acute Hemangioma-like lesions associated with echo viral infections. Pediatr 1969; 44(4):198-502.

3. Prose N, Tope W, Miller S, Kamino H. Eruptive pseudoangiomatosis: A unique childhood exanthem?. J Am Acad Dermatol 1993; 29(5):857-859.

4. Calza A, Saurat J. Eruptive pseudoangiomatosis: A unique childhood exanthem? J Am Acad Dermatol 1994; 31(3):517-518.

5. Neri I, Patrizi A, Guerrini V, Ricci G, Cevenini R. Eruptive Pseudoangiomatosis. Br J Dermatol 2000; 143:435-438.

6. Guillot B, Dandurand M. Eruptive pseudoangiomatosis arising in adulthood: 9 cases. Eur J Dermatol 2000; 10:455-458.

7. Frieden, I. Childhood exanthems. Curr Opin in Pediatr 1995; 7:411-414.

8. Mancinci, A. Exanthems in childhood: An update. Pediatr Ann 1998; 27:163-170.

9. Balfour H. Fifth Disease: Full fathom five. Am J Dis Child 1976; 130:239-240.

10. Levy R, Weissman A, Blomberg G, Hagay ZJ. Infection by parovirus B19 during pregnancy: A review. Obstet Gynecol Surv 1997; 52(4):254-9.

11. Crowcroft N, Roth, CE, Cohen B, Miller E. Guidance for control of parvovirus B19 infection in healthcare settings and the community. J of Pub Health Med 1999; 21(4):439-466.

12. Committee on Infectious Diseases, American Academy of pediatrics. Parvovirus B19. In:Peter G, editor. Red book. 24th ed. Elk Grove Village, Ill. Amer Acad of Pediatr; 1997. p. 383-385.

13. Anand A, Gray E, Brown T, Clewley J, Cohen B. Human Parvovirus infection in pregnancy and hydrops fetalis. The N Engl J of Med 1987; 316(4):183-186.

14. Center for Disease Control and Prevention. Risks Associated with human parvovirus B19 infection. MWWR Morb Mortal Wkly Rep. 1989; 261(11):1555-1560.

15. Mankuta D, Bar-Oz B, Koren G. Erythema infectiosum (Fifth disease) and pregnancy. Motherisk 1999; 45:603-605.

16. Hall C, Horner F. Encephalopathy with Erythema infectiosum. Am J Dis Child 1977; 131:65-67.

17. Shimizu Y, Ueno T, Komatsu H, Takada H, Nunoue T. Acute cerebellar ataxia with human parvovirus B19 infection. Arch Dis Child 1999; 80:72-73.

18. Hofmann B, Schuppe HC, Adams O, Lenard HG, Lehmann P, Ruzicka T. Gianotti-Crosti syndrome associated with Epstein-Barr virus infection. Pediatr Dermatol 1997; 14(4):273-277.

19. Smith K, Skelton H. Histopathologic features seen in Gianotti-Crosti syndrome secondary to Epstein-Barr virus. J Am Acad Dermatol 2000; 43(6):1076-1079.

20. Caputo R, Gelmetti C, Ermacora E, Gianni E, Silvestri A. Gianotti-Crosti syndrome: A retrospective analysis of 308 cases. J Amer Acad of Derm 1992; 20(1):207-210.

21. Baleviciene G, Maciulevicine R, Schwartz R. Papular Acrodermatitis of Childhood: The Gianotti-Crosti syndrome. Pediatr Dermatol 2001; 67:291-294.

22. Andiran N, Senturk G, Bukilmez G. Combined vaccination by measles and hepatitis B vaccines: A cause of Gianotti-Crosti syndrome. Dermatol 2002; 204:75-76.

23. Chuh A. Diagnostic criteria for Gianotti-Crosti syndrome: A prospective case-control study for validity assessment. Cutis 2001; 68:207-213.

24. Tindall J, Miller G. Hand, foot and mouth disease. Cutis 1972; 9:457-463.

25. Graham B. Hand, foot, and mouth disease. EMedicine Journal 2002; 3(2):1-10.

26. Huang C, Liu C, Chang Y, Chen C, Wang S, Yeh TF. Neurologic complications in children with enterovirus 71 infection. The N Engl J of Med 1999; 341(13):936-942.

27. Liu C, Tseng HW, Wang SM, Wang JR, Su IJ. An outbreak of enterovirus 71 infection in Taiwan, 1998: Epidemiologic and clinical manifestations. J of Clin Virol 2000; 17:23-30.

28. Shelley W, Hashim M, Shelley E. Acyclovir in the treatment of hand-foot-and-mouth disease. Cutis 1996; 57:232-234.

29. Cole RM. Studies of Coxsackie viruses: Observations on epidemiological aspects of group A viruses. Am J Pub Health 1951; 41:1342.

30. Cherry JD, Jahn CL. Herpangima: Etiologic Spectrum. Pediatr 1965; 36:632.

31. Freedberg, I. Fitzpatrick's Dermatology in General Medicine. 5th Ed. McGraw-Hill Companies, Inc 1999. p. 2407-2409; 2398-2403.

32. Markowitz L, Prebuld S, Orenstein W, Rovira E, Adams N, Hawkins C, Hinman A. Patterns of transmission in measles outbreaks in the United States, 1985-1986. The N Engl J of Med, 1989; 320(2):75-81.

33. Center for Disease Control and Prevention. Measles-United States, 2000.MWWR Morb Mortal Wkly Rep; 287(9):1105-1106.

34. Hussey G, Klein M. A Randomized, controlled trial of vitamin in children with severe measles. The N Engl J of Med 1990; 323(3):160-164.

35. Caballero B, Rice A. Low serum retinal is associated with increased severity of measles in New York City children. Nutrition Reviews 1992; 50(10):291-292.

36. Harms M, Feldman R, Saurat JH. Papular-purpuric "gloves and socks" syndrome. J Am Acad Dermatol 1990; 23:850-4.

37. Bagot M, Revuz J. Papular-purpuric "gloves and sock" syndrome: Primary infection with parvovirus B19. JAAD 1991; 25:341.

38. Halasaz C, Cormier D, Den M. Petechial glove and sock syndrome caused by parvovirus B19. J Am Acad Dermatol 1192; 27:835-8.

39. Smith P, Landry M, Carey H, Krasnoff J, Cooney E. Papular-purpuric gloves and socks syndrome associates with acute parvovirus B19 infection: Case report and reviews. Clin Infect Dis 1998; 27:164-8.

40. Ferroils A, Martinez-Aparicio A, Aliaga-Boniche A. Papular-purpuric "gloves and socks" syndrome caused by measles virus. J Am Acad Dermatol 1994; 30:291-292.

41. Feldman R, Harms M, Saurat JH. Papular-Purpuric 'Gloves and Socks' syndrome: Not only Parvovirus B10. Dermatol 1994; 188:85-87.

42. Carrascosa JM, Bielsa I, Ribera M, Ferrandiz C. Papular-purpuric gloves-and-socks syndrome related to cytomegalovirus infection. Dermatol 1195; 1991:269-270.

43. Guibal F, Buffet P, Mouly F, Morel P, Rybojad M. Papular-purpuric gloves and socks syndrome with hepatitis B infection. Lancet 1996; 347:473.

44. Veraldi S. Papular-purpuric 'Gloves and Socks syndrome. Arch Dermatol 1996; 132:975-979.

45. Drago F, Parodi A, Rebora A. Gloves-and-Socks syndrome in a patient with Epstein-Barr virus infection. Dermatol 1997; 194:374.

46. Ruzicka T, Kalka K, Diercks K. popular-Purpuric 'Gloves and Socks' syndrome associated with human herpesvirus 6 infection. Arch Dermatol 1998; 134:242-244.

47. Grilli R, Izquierdo MJ, Farina MC, Kutzner H, Gadea I, Martin L, Requena L. Papular-purpuric "gloves and socks" syndrome:Polymerase chain reaction demonstration of parvovirus B19 DNA in cutaneous lesions and sera. J Am Acad Dermatol 1991; 41(5):793-796.

48. Feldmann R, Harms M, Saurat JH. Papular-purpuric "gloves and socks" syndrome: not only parvovirus B19 infection. Dermatology 1994; 188:85-87.

49. Stone MS, Murph JR. Papular-Purpuric Gloves and Socks syndrome: A characteristic viral exanthem. Pediatr 1993; 92:864-865.

50. Nelson JSB, Stone MS. Update on selected viral exanthems. Curr Opin in Pediatr 2000; 12:359-364.

51. Kempf W, Burg G. Pityriasis rosea-a virus-induced skin disease? An update. Arch Virol 2000; 1509-1520.

52. Drago F, Ranieri E, Malaguti F, Battifoglio ML, Losi E, Rebora A. Human herpesvirus & in patients with pityriasis rosea. Dermatol 1997; 195:374-378.

53. Kempf W, Adams V, Kleinhans M, Burg G, Panizzon R, Campadelli-Fiume G, Nestle F. Pityriasis rosea is not associated with human herpesvirus 7. Arch Dermatol, 1999; 135:1070-1072.

54. Offidani A, Pritelli E, Simonetti O, Cellini A, Giornetta L, Bossi G. Pityriasis rosea associated with herpesvirus 7 DNA. JEADV 2000; 14, 313-314.

55. Kosuge H, Tanaka-Taya K, Miyoshi H, Amo K, Harada R, Ebihara T, Kawahara Y, Yamanishi K, Nishikawa T. Epidemiological study of human herpesvirus-6 and herpesvirus-7 in pityriasis rosea. Br J Dermatol 2000; 143:795-798.

56. Drago F, Rebora A. Pityriasis rosea: One virus, two viruses, more viruses? Br J Dermatol 2001; 144:1090.

57. Chuh A.A.T. Rash orientation in pityriasis rosea: A qualitative study. Eur J Deramtol 2002; 12:253-256.

58. Sharma Prafulla, Yadav Tribhuvan, Gautam Ram, Taneja Neelam, Satyanarayana L. Erythromycin in pityriasis rosea: A double-blind, placebo-controlled clinical trial. J Am Acad Dermatol 2000; 42:241-244.

59. Chuh A.A.T., Chan H.H.L. Prospective case-control study of chlamydia legionella and mycoplasma infections in patients with pityriasis rosea. Eur J Dermatol 2002; 12:170-173.

60. Berenber W, Wright S, Janeway C. The N Engl J Med 1949; 241(7):253-259.

61. Altschuler E. Oldest description of roseola and implications for the antiquity of human herpesvirus 6. The Pediatr Infect Dis J 2000; 19(9):903.

62. Yamanishi K, Okuno T, Shiraki K, Takahashi M, Kondo T, Asano Y, Kurata T. Identification of human herpesvirus-6 as a casual agent for exanthem subitum. Lancet 1988; 1065-1067.

63. Stoeckle M. The spectrum of human herpesvirus 6 infection: from roseola infantum to adult disease. Annu Rev Med 2000; 51:423-430.

64. Kondo K, Nagafuji H, Tomomori C, Yamanishi K. Association of human herpesvirus 6 infection of the central nervous system with recurrence of febrile convulsions. J Infect Dis 1993; 167(5):1197-2000.

65. Ohta H, Watanabe Y, Sumimoto S, Kojima N, Ishigaki T, Todo G, Nii M. Hypoperfusion of right hemisphere with exanthem subitum and left hermparesis. Ann Nucl Med 2000; 14(3):223-225.

66. van den Berg JS, van Zeijl JH, Rotteveel JJ, Melchers WJ, Gabreels FJ, Galama JM. Neuroinvasion by human herpesvirus type 7 in a case of exanthem subitum with severe neurologic manifestations. Neurol 1999; 52(5)1077-1079.

65. Hashimoto H, Maruyama H, Fujimoto K, Sakaura T, Seishu S, Okuda N. Hematologic findings associated with thrombocytopenia during the acute phase of exanthem subitum confirmed by primary human herpesvirus-6 infection. J of Pediatr Hematol/Oncol 2002; 24:211-214.

68. Andrews' Diseases of the Skin, 9th edn. Rubella. WB Saunders Co. USA 2000:506.

69. Reef S, Frey T, Theall K, Abernathy E, Burnett C, Icenogle J, McCauley M, Wharton M. The changing epidemiology of rubella in the 1990's. JAMA 2002; 287(4):464-472.

70. Fine JD, Arndt K. The TORCH syndrome: A clinical review. J Am Acad Dermatol 1985; 12:697-706.

71. Sheridan E, Aitken C, Jeffries D, Hird M, Thayalasekaran P. Congenital rubella syndrome; a risk in immigrant populations. Lancet 2002; 359:674-675.

72. Center for Disease Control and Prevention. Acute flaccid paralysis associated with circulating vaccine-derived poliovirus-Philippines. MWWR Morb Moral Wkly Rep 2001; 287(3):311.

73. Brunner M, Rubin L, Dunlap F. A new popular erythema of childhood. Arch Dermatol 1962; 85:147-148.

74. Bodemer C, de Prost Y. Unilateral laterothoracic exanthem in children: A new disease? J Am Acad Dermatol 1992; 27:693-696.

75. Coustou D, Leaute-Labreze C, Bioulac-Sage P, Labbe L, Taieb A. Asymmetric periflexural exanthem of childhood. Arch Dermatol 1999; 135:799-803.

76. Taieb A, Megraud F, Legrain V, Mortureux P, Maleville J. Asymmetric periflexural exanthem of childhood. J Am Acad Dermatol 1993; 29:391-393.

77. McCuaig C, Russo P, Powell J, Pedneault L, Lebel P, Marcoux D. Unilateral laterothoracic exanthem. J Am Acad Dermatol 1996; 34:979-984.

© 2003 Dermatology Online Journal