Exanthem Break Out

Confusing Terms

Exanthem = A widespread eruptive rash associated with a systemic disorder, typically caused by a virus but can also occur in the presence of bacteria, drug, toxin or autoimmune disease

  • Etymology: 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.
  • Exanthem are more common in children than in adults.
    • Common types: maculopapular, papular, vesicular, petechial/purpuric, urticarial, pustular  

Viruses that commonly cause exanthems include measles (morbillivirus), rubella (rubella virus), varicella (varicella zoster virus), erythema infectiosum (parvovirus B19), roseola (human herpesvirus 6), hand foot and mouth disease (coxsackievirus A16), and even COVID-19 (coronavirus).

Many viral exanthems are known by more than one name:

  • Measles = Rubeola
  • Rubella = German measles
    • Fun (and confusing) fact: In Spanish, rubella is la rubeola whereas measles (aka rubeola in English) is el sarampión
  • Erythema infectiosum = Fifth disease
    • The name “fifth disease” comes from its place on the (outdated) standard list of rash-causing childhood diseases, which also includes measles (first disease), scarlet fever (second), rubella (third), Dukes’ disease (fourth, but no longer accepted as distinct from scarlet fever), and roseola (sixth). Of these terms, only fifth disease remains in use.
  • Roseola = Exanthem subitum
  • Varicella = Chickenpox

Measles

In general, measles presents with a prodrome followed by a characteristic enanthem, which is followed by a characteristic exanthem.

Source: Moss WJ. Lancet. 2017

Prodrome = fever, malaise, and anorexia, which then progresses to at least one of the 3 C’s: conjunctivitis (nonpurulent), coryza, and cough

  • Prodrome typically lasts 2-4 days, but possibly longer
  • Coryza = inflammation of the mucous membranes lining the nasal cavity, usually causing a running nose, nasal congestion and loss of smell

Enanthem = Koplik spots (1-3 mm whitish, grayish, or bluish elevations with an erythematous base, typically seen on the buccal mucosa opposite the molar teeth, though they can spread to cover the buccal/labial mucosa and hard/soft palate)

Exanthem = Maculopapular/morbilliform rash that often coalesces

Clinical improvement typically ensues within 2 days of the rash’s appearance. After 3-4 days, the rash typically darkens and begins to fade, followed by fine desquamation in the more severely involved areas. The rash usually lasts ~7 days and fades in the order it appeared.

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Clinical complications (more common in infants, pregnancy, immunocompromise, and vitamin A deficiency):

  • Early: otitis media, pneumonia, laryngotracheobronchitis (croup), diarrhea, keratoconjunctivitis (rare), ADEM (rare)
    • Pneumonia and diarrhea account for the majority of measles-related morbidity and mortality
  • Late: immunosuppression, measles inclusion body encephalitis (rare; occurs within 1 year of initial infection), subacute sclerosing panencephalitis (rare; occurs 7-11 years later)

“Children who have had measles have long-term blunted immune responses to other pathogens and increased mortality attributable to the known effects of measles virus on lymphocytes.”

Red Book, 32nd Ed.

Rubella

In general, postnatal rubella infections are mild—many patients are asymptomatic.

Source: Winter AK, Moss WJ. Lancet. 2022

Prodrome = Low-grade fever and lymphadenopathy (LAD) may occur concurrently or 1-5 days prior to the appearance of the exanthem

LAD typically involves the posterior cervical, postauricular, and suboccipital lymph nodes, often lasting 5-8 days.
Source: The Royal Children’s Hospital Melbourne
  • Other potential symptoms include headache, nonpurulent conjunctivitis, rhinorrhea, small red spots on the soft palate (Forchheimer spots), polyarthralgia, and malaise.

Exanthem = Generalized maculopapular rash (often pinpoint pink lesions)

  • First appears on the face, spreads caudally to the trunk and extremities while sparing the palms and soles
  • Often becomes generalized within 24 hours and fades within 3 days

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Clinical complications:

  • Acute encephalitis (rare)
  • Thrombocytopenia (rare)

Varicella

Varicella-zoster virus (VZV) is a type of herpesvirus that causes 2 clinically distinct forms of disease: varicella (chickenpox) and herpes zoster (shingles).

  • Primary VZV infection results in the diffuse vesicular rash of varicella, which is generally mild in children but more severe in adults or immunocompromised patients of any age
  • Endogenous reactivation of latent VZV can result in the localized skin infection of herpes zoster

Prodrome = fever, malaise, pharyngitis, and/or loss of appetite, followed by the development of a generalized vesicular rash usually within 24 hours

Exanthem = Pruritic vesicular rash that appears in successive crops over several days

  • Lesions are polymorphic that rapidly evolve from macules/papules to vesicles then pustules, which crust; lesions start on the face and scalp, then progress to the trunk (highest density) and extremities, sparing the palms and soles
  • Patients typically have lesions in different stages of development at the same time
  • New vesicle formation usually stops within 4 days of rash onset, and most lesions have fully crusted by day 6 in patients who are not immunocompromised
  • Crusts tend to fall off within 1-2 weeks

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Clinical complications:

  • Soft tissue infections (most often GAS or S.aureus)
  • Pneumonia (more common in adults)
  • Acute cerebellar ataxia
  • Encephalitis (rare)
  • Intracranial vasculitis (rare, occurring months after infection)

Erythema Infectiosum

Parvovirus has a wide range of clinical manifestations. Erythema infectiosum is typically a mild febrile illness followed by a characteristic rash, and most often occurs in children.

Prodrome = Fever, coryza, headache, nausea, and diarrhea, followed by exanthem 2-5 days later

Exanthem = Edematous erythematous plaques on the cheeks (“slapped cheek appearance”), followed by erythematous lacy eruption on the body several days later

  • The rash is thought to be immunologically mediated, and by the time it appears, viremia has resolved and the patient usually feels well; nevertheless, the rash may persist for 1-3 weeks, exacerbated by environmental factors including sunlight and heat
  • In adults, the rash is less specific and may be morbilliform, confluent, or vesicular

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Clinical complications:

  • Transient aplastic crisis
  • Acute encephalitis

Roseola

Roseola is typically a self-limited illness characterized by a few days of high fever followed by a rash.

Prodrome = 3-5 days of high fever, irritability, and LAD (although children are typically otherwise active and well-appearing)

Exanthem = Blanching macular or maculopapular rash starting on the neck and trunk then spreading to the face and extremities, and often lasting no more than 1-2 days

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Complications:

  • Seizures
  • Aseptic meningitis
  • Acute encephalitis
  • Thrombocytopenic purpura

Hand Foot & Mouth Disease

Hand, foot, and mouth disease (HFMD) is one of the most recognizable viral exanthems/enanthems in children and adults. Prodromal symptoms are not always present.

  • Though similar, HFMD is technically distinct from herpangina, which causes clusters of painful papulo-vesiculo-ulcerative lesions only in the mouth. Nevertheless, the enanthem of HFMD may occur without the exanthem and the exanthem may occur without the enanthem.

Prodrome = Low-grade fever, sore throat, and/or malaise, typically lasting a few days prior to rash onset (usually first the enanthem shortly followed by exanthem)

Enanthem = Painful, punched-out vesicles on the hard palate, tongue and buccal mucosa

Exanthem = Non-pruritic macular, maculopapular, and/or vesicular lesions on the distal extremities, buttocks, and upper thighs, typically lasting 3-4 days

  • Lesions typically begin as erythematous macules that progress to vesicles surrounded by a thin erythematous halo; vesicles quickly rupture and form superficial ulcers with a gray-yellow base and an erythematous rim
  • Months later, as a result of changes in the nail matrix, patients can develop nail changes including Beau’s lines (transverse lines across the nail) and onychomadesis (transverse splitting of the nail leading to nail plate shedding)

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Complications from HFMD are uncommon but may occur when the underlying cause is enterovirus 71, which may lead to rhombencephalitis, acute flaccid paralysis, aseptic meningitis, pulmonary edema/hemorrhage, and heart failure.

Blog post based on Med-Peds Forum talk by Tabitha Ndung’u, PGY-1, and Cecilia Paasche, PGY-1

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