Characterizing Viral Exanthems
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For reprint orders, please contact: [email protected] Characterizing viral exanthems Joseph M Lam† An exanthem is any eruptive skin rash that may be associated with fever or other systemic symptoms. Causes include infectious pathogens, medication reactions and, occasionally, a combination of both. In children, exanthems are most often related to infection and, of these, viral infections are the most common. Some exanthems have very specific morphologies that help identify and characterize the eruption. In this article, we describe common and uncommon viral exanthems, based on their morphology, and review current advancements in understanding and treatment of these exanthems. An exanthem is any eruptive skin rash that 10–12 days, and clinical disease begins with may be associated with fever or other systemic symptoms of fever, conjunctivitis, rhinorrhea, symptoms. Causes include infectious patho- sore throat and a dry cough. Koplik spots (gray– gens, medication reactions and, occasionally, a white papules on the buccal mucosa) may be seen combination of both. during this prodromal phase. Approximately Over 100 years ago, a group of characteristic 3–4 days after the prodromal symptoms, the childhood eruptions were described and num- typical exanthem of coalescing erythematous bered from one to six [1,2]: measles, scarlet fever, macules and papules erupts, beginning behind rubella, erythema infectiosum and roseola infan- the ears and in the hairline area, and spreads over tum. The origin of the fourth classic childhood the rest of the skin over a period of a few days. eruption, formerly referred to as Dukes’ disease, The eruption typically resolves in the same order is controversial. It may represent misdiagnosed as its appearance, and will often desquamate. cases of rubella or scarlet fever, rather than a The differential diagnosis includes other distinct illness. maculopapular exanthems, such as rubella, Viral exanthems are common in childhood. toxic shock syndrome, roseola, parvovirus B-19 The words ‘exanthema’ and ‘anthos’ mean infection and drug eruptions. Complications of ‘breaking out’ and ‘flower’ in Greek, respectively. measles include transient immunosuppression, Similarly, a child breaking out with a viral exan- acute postinfectious encephalitis and subacute them may be likened to a flower bursting into sclerosing panencephalitis (SSPE). Transient bloom. In children, exanthems are most often immunosuppression occurs during the ill- related to infection [3] and, of these, viral infec- ness and lasts for approximately 6 weeks [1] . tions are the most common. Determining the During this time, an infected individual is at cause of an exanthem is based on the character- risk for secondary bacterial infections, such istic morphology, distribution and time course as otitis media, pneumonia or gastroenteritis. of the eruption, as well as a careful assessment Postinfectious encephalitis occurs in approxi- of infectious contacts, immunization status and mately one in 1000 patients, and manifests aspects of the physical examination. Although approximately 1 week after the onset of the not always diagnostic, the morphology and exanthem [4]. Symptoms present during, or configuration of cutaneous lesions are of con- shortly after, acute infection, and include head- †Departments of Paeditrics & Dermatology, University of British siderable importance to the classification and ache, fever and seizures. A lesser-known entity, Columbia, 1803–1805 West Broadway, diagnosis of viral exanthems. For the purpose known as measles inclusion-body encephalitis, Vancouver, BC, V5Z 1K1, Canada Tel.: +1 604 876 4433 of this article, we will characterize common can affect immunocompromised patients from Fax: +1 604 876 4431 [email protected] and uncommon viral exanthems, based on their weeks to months after acute infection [5]. SSPE morphology, and will discuss current advance- affects approximately one in 100,000 patients, ments in understanding and treatment of these and manifests as a slow, progressive disease, Keywords viral diseases. which can present months or even years after resolution of the acute infection. The onset of • dermatology • exanthem • virus Macular & maculopapular exanthems SSPE is insidious, and psychiatric manifesta- Measles tions are prominent. Subsequently, myoclonic Measles is caused by a ssRNA virus belonging to seizures usually lead to a final stage of akinetic part of the Paramyxoviridae family, genus Morbillivirus. mutism. In total, 95% of individuals with It has an incubation period of approximately SSPE die within 5 years of diagnosis [6]. SSPE 10.2217/PHE.10.66 © 2010 Future Medicine Ltd Pediatric Health (2010) 4(6), 623–635 ISSN 1745-5111 623 – Lam is caused by a persistent infection of the CNS B19 comes from the bloodbank code, where with the virus, and early childhood infection the original positive serum sample was labeled with measles is a risk factor for SSPE. (i.e., Row B, Sample 19) [12] . It is the only parvo- An unusual variant of measles can be seen in virus that has been linked directly to disease in previously vaccinated individuals, infants with humans [13] . Although parovirus B19 infection maternal IgG antibodies and patients on immu- can have different clinical manifestations (see noglobulin therapy [1] . In this modified form, later), EI is the most commonly recognized. the prodrome and exanthem are milder and of Erythema infectiosum manifests in three shorter duration. However, the disease is just overlapping stages. After an incubation period as contagious in these individuals. Diagnosis of 1–2 weeks, patients present with fiery-red is based on clinical presentation with labora- facial erythema, which has been described as tory confirmation, if necessary. Measles IgM having a ‘slapped cheeks’ appearance (FIGURE 1). can usually be detectable after the first 3 days In the second stage, patients develop a reticulate of the exanthem. macular or urticarial exanthem 1–4 days after Currently, there is no specific antiviral ther- the slapped cheek eruption, and this second rash apy for measles and treatment is symptomatic. is mainly seen over the proximal extremities. More importantly, the longstanding availabil- In the third stage, the exanthem recurs inter- ity of the measles vaccine makes the disease mittently in response to stimuli, such as local easily preventable. Despite, this, there is still irritation, high temperatures and emotional poor uptake of the vaccine [7–9], owing to, in stress [12] . Arthropathy may occur in up to part, a proposed causal relationship between 60% of adults with EI [14], whereas it will only receipt of the measles–mumps–rubella vaccine occur in approximately 10% of children with and autism, a claim that has been convincingly joint symptoms. In children, the arthro pathy scientifically refuted [10] . affects larger joints, such as the knees, wrists and ankles, and in an asymmetric pattern [12] . Rubella The differential diagnosis includes a drug Rubella, or German measles, is caused by reaction, measles, rubella and enterovirus infec- an RNA virus in the Togaviridae family. tion, and roseola infantum. Complications of Approximately 50% of infected individuals EI are owing to the affinity of parvovirus B19 become symptomatic. After an incubation for erythroid precursors. Parvovirus B19 infec- period of 2–3 weeks, symptomatic patients tion can suppress red blood cell production, exhibit prodromal symptoms, which include causing transient aplastic crisis, chronic red cell low-grade fever, headache, sore throat and aplasia, hydrops fetalis or congenital anemia. myalgias. A macular or maculopapular exan- This is even more likely in patients with ill- them appears after approximately 2–5 days and nesses that have already shortened the lifespan spreads in a cephalocaudal pattern. Symmetrical of erythrocytes, such as iron-deficiency ane- lymphadenopathy is often seen, and often mia, HIV, sickle cell disease, thalassemia and occurs in the postauricular and occipital areas. sphero cytosis. Although treatment is support- Arthralgias and arthritis are also common. The ive, at-risk patients may require transfusions or most serious complication of rubella is congen- intravenous immunoglobulin therapy [15,16] . tial rubella syndrome, which classically presents The diagnosis of EI is usually made clinically. with the triad of deafness, cataracts and cardiac An ELISA is commercially available with high disease [11] . The differential diagnosis includes sensitivity, although false-positive results may other maculopapular exanthems, such as mea- recur owing to crossreaction to other viruses or sles, roseola, parvovirus B-19 infection and the rheumatoid factor [17] . PCR can detect viral drug eruptions. The diagnosis of rubella can DNA in clinical samples of urine, respiratory be made with IgM antibody titers. Patients are secretions, body tissues and serum [18] . contagious 1 week prior to the eruption of the rash until a week after the rash resolves. The Roseola infantum treatment of rubella is supportive. Roseola infantum is caused by human her- pesvirus (HHV) types 6 and 7, and belongs Erythema infectiosum to the Roseolovirus genus in the subfamily Erythema infectiosum (EI) is a common child- of Betaherpesvirinae [19] . hood exanthematous illness caused by parvo- Both HHV-6 and -7 are highly prevalent in virus B19 – a nonenveloped, ssDNA virus the healthy population, and establish latency belonging to the Parvoviridae family. The name in macrophages and T lymphocytes. They are