The term "exanthem" is derived from the Greek "exanthema," which translates to "breaking out," and is used to describe cutaneous eruptions that arise abruptly and on several skin surfaces at once. In contrast, "enanthem" refers to mucous membrane involvement. Several viral infections are associated with viral exanthems and/or enanthems. Many of the cutaneous and mucosal findings of these infections are nonspecific in nature, but key aspects of the clinical history and presentation can suggest select etiologies.

During spring and winter, nonspecific eruptions can be seen with upper respiratory illnesses, often due to parainfluenza viruses, respiratory syncytial viruses, rhinovirus, and type A and B influenza virus. These are generally morbilliform in appearance and last for up to 2 days, and largely occur in children. Petechial lesions can also be seen in influenza and enteroviral infections when generalized.

The classic childhood diseases that cause viral exanthems were originally named numerically for the order in which they were discovered. Second disease (scarlet fever) is secondary to a bacterial infection and will not be covered in this section. Fourth disease is no longer felt to represent a distinct entity. Measles and rubella have largely been prevented by vaccination in industrialized countries; however, suspicion must remain high given the recent trend towards refusing childhood vaccination and in the case of nonimmunized migrants.

First disease (measles, rubeola) occurs secondary to paramyxovirus. After 10-14 days, a prodrome of fever, dry cough, coryza, and conjunctivitis (often with photosensitivity) occurs, with development of Koplik spots (gray-white papules on the buccal mucosa) approximately 2 days prior to cutaneous symptoms. Cutaneous lesions begin on the head and proceed in a cephalocaudal progression. Petechial, vesicular, and purpuric lesions have been described in association with atypical measles. The rash fades after about 5 days in a cephalocaudal fashion. Patients are contagious for about 4 days prior to and after the exanthem.

Third disease (rubella, German measles) occurs secondary to togavirus. After 2-3 weeks, a prodrome of fever, headache, malaise, and lymphadenopathy (characteristically involving the occipital and post-auricular lymph nodes) occurs. This is followed by an exanthem that spreads in a cephalocaudal fashion and fades more rapidly than measles, occurring over 3 days. Punctate erythematous spots over the uvula and soft palate (Forchheimer sign) can also be seen.

Fifth disease (erythema infectiosum) occurs secondary to parvovirus B19. It is most commonly noted in patients between 4 and 10 years of age and involves a "slapped cheek" appearance of the cheeks with circumoral pallor. After 1-4 days, a lacy reticular eruption on extensor surfaces arises that lasts up to 3 weeks. This eruption commonly waxes and wanes in intensity in response to local irritation, emotional stress, and high temperatures.

Sixth disease (roseola, exanthem subitum) occurs secondary to human herpesvirus (HHV)-6 or HHV-7 and occurs in patients younger than 2 years of age. A prodrome of high fever in an otherwise well child occurs for up to 5 days, followed by a sudden defervescence and appearance of rose-pink macules and papules with white halos (subitum is Latin for "suddenly"). The presence of this exanthem marks the end of viremia. Palpebral and periorbital edema (Berliner's sign) may be seen.

There are other presentations of these viruses in this age group. Pityriasis rosea occurs secondary to HHV-6 and HHV-7 and is characterized by a prodrome marked by the appearance of a single, scaly pink plaque called the herald patch, followed by the eruption of several pink, oval, thin papules with a leading border of scale in a "Christmas-tree" pattern. Lesions resolve in weeks to months. Papular purpuric gloves and socks syndrome (PPGSS) occurs secondary to parvovirus B19 and typically occurs in young adults but cases have been reported in children. It is characterized by symmetric purpuric or painful edema and erythema that progress to purpuric papules and petechiae. The lesions burn and itch and are sharply marginated at the ankles and feet. Oral lesions can be seen, including oral erosions, vesicles, swollen lips, and petechial of hard palate, pharynx, and tongue. The exanthem resolves in 1-2 weeks.

The presence of vesicular lesions can raise concern for varicella-zoster virus (VZV), herpes simplex virus (HSV), hand-foot-and-mouth disease (HFMD), and herpangina.

The presence of localized lesions raises suspicion for unilateral laterothoracic exanthem, which affects children 6 months to 10 years of age. Lesions arise unilaterally around the axillary vault or inguinal crease before progressing to demonstrate bilateral involvement. Lesions are initially papular but progress to an eczematous appearance. Cutaneous lesions resolve over a period of weeks to months.

Epstein-Barr virus (EBV) can also present as lymph node enlargement, yellow or gray tonsillar pseudomembrane, palatal petechiae, maculopapular or petechial eruption, splenomegaly, and hepatomegaly. A diffuse morbilliform eruption can also be seen following administration of amoxicillin or ampicillin. Notably, very painful, >1 cm genital ulceration can be seen (Lipschütz ulcers) in pre-adolescent females, often with a necrotic appearance and violaceous borders, involving the labia majora, labia minora, or inner thighs. "Kissing lesions" with a symmetric appearance are seen.

Exanthems and/or enanthems have been reported with COVID-19 and multisystem inflammatory syndrome in children. See skin and oral mucosal manifestations of COVID-19 for further details.