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1Medical Student Core Curriculum in Dermatology Viral ExanthemsMedical Student Core Curriculumin DermatologyLast updated March 16, 2011
2Goals and ObjectivesThe purpose of this module is to help medical students develop a clinical approach to the evaluation and initial management of patients presenting with typical viral exanthems.By completing this module, the learner will be able to:Recognize morbilliform eruption as a prototype for viral exanthemsDescribe classic presentations of distinctive pediatric viral exanthemsProvide counseling for parents of children with typical viral exanthems
3Definitions Exanthem (exanthema) Enanthem (enanthema) A rash that appears abruptly and affects several areas of the skin simultaneouslyGreek origin “exanthema” which means “a breaking out”Enanthem (enanthema)An eruption upon a mucous membrane
4Viral ExanthemsCommonly described as “morbilliform” which means “composed of erythematous macules and papules that resemble a measles rash.”Viral exanthems can be difficult to distinguish from a drug eruption. However, viral exanthems are more common in children, and drug eruptions tend to be more common in adults. A thorough history will aid in the diagnosis.
6Classic Childhood Exanthems Historically, there were six childhood exanthems whose etiologies are now well-defined:NUMBERNAMEETIOLOGYFirst DiseaseMeasles (Rubeola)Measles virusSecond DiseaseScarlet FeverStreptococcus pyogenesThird DiseaseRubellaRubella virusFourth DiseaseDuke’s DiseaseNo longer accepted as a distinct disorderFifth DiseaseErythema InfectiosumParvovirus B19Sixth DiseaseRoseola InfantumHHV-6 and HHV-7
8Case One: HistoryAna is 4-year-old previously healthy girl who presents with a 1 week history of cough, runny nose, fever, sore throat and red eyes. She went to her pediatrician 2 days ago and was prescribed Augmentin (amoxicillin and clavulanate) for presumed pharyngitis.Yesterday, Ana developed a red rash which started on her face and has spread to her trunk. Her mother would like to know if the rash is from her new medication.
9History ContinuedUpon further questioning you discover that Ana has never received vaccinations due to her mother’s fear regarding autism.The augmentin was started 24 hours before the onset of her rash.You also discover that a close family member recently visited from the Netherlands, who also developed a similar rash.
10Case One: Skin ExamAna is an ill-appearing child who presents with a morbilliform rash with erythematous macules and papules.Lesions have coalesced on the face and neck.Rash has spread to her trunk and extremities (not shown)SDC: could use better picture
11Exam ContinuedInspection of Ana’s mouth reveals, bluish-white dots on the mucosal surface. These are called Koplik spots.
13Case One, Question 1Based on the history and exam, what is the most likely diagnosis?Drug EruptionErythema InfectiosumMeaslesRoseolaRubella
14Case One, Question 1 Answer: c Based on the history and exam, what is the most likely diagnosis?Drug Eruption (Too soon for an exanthematous drug eruption. Refer to the module on drug reactions for more information)Erythema Infectiosum (Eruption begins with bright red cheeks followed by a reticular eruption on the trunk and extremities)MeaslesRoseola (Tends to occur in younger children with high fevers preceding a sudden rash that begins on the trunk)Rubella (Rash tends to spread more quickly, covering the body in 24hrs)
15Measles (Rubeola) Measles is a viral disease Spread by respiratory dropletsIncubation period tends to be 8-12 days from exposure to onset of symptomsPatients are contagious from 1-2 days before onset of symptoms (3-5 days before the rash) to 4 days after appearance of the rashImmunocompromised patients can be contagious for the duration of the illness
16Measles (Rubeola) Most common in children 3-5 years old Incidence of measles has decreased substantially where measles vaccination has been institutedMost cases of measles in the United States are imported with spread to unvaccinated individualsMeasles is still common in many developing countries (parts of Africa and Asia) and outbreaks repeatedly occur in communities who do not accept vaccinations (e.g. religious community in Netherlands)
17Measles: Clinical Presentation Prodrome: Fever, Malaise, Conjunctivitis, Cough, Coryza*, Koplik spotsExanthem: Erythematous macules and papules begin on the face and spread cephalocaudally and centrifugally (by the 3rd day, the whole body is involved).Recovery: Clinical improvement begins within 2 days of appearance of the rash. The rash tends to fade after 3-4 days and will last around 6-7 days.*Coryza: “head cold” with nasal congestion, rhinorrhea, sore throat
18DiagnosisMeasles is a distinct clinical syndrome with the presence of high fever, Koplik spots, characteristic conjunctivitis, upper respiratory symptoms, and typical exanthem.All cases of suspected measles should be serologically confirmed and reported immediately to the local or state health department without waiting for results of diagnostic tests.Testing includes:Serology: Anti-measles IgM and IgG, isolation of measles virus or identification of measles RNAHistologic evaluation of skin lesions or respiratory secretions may show syncytial keratinocytic giant cells
19Case One, Question 2Which of the following statements about the treatment of measles is correct?No specific antiviral therapy is recommended for immunocompetent patients with measles.Prevention of the spread of measles depends on prompt immunization of people at risk for exposure or people already exposed who cannot provide documentation of measles immunityRecommend supportive care with antipyretics, fluids, and rest.All of the above
20Case One, Question 2 Answer: d Which of the following statements about the treatment of measles is correct?No specific antiviral therapy is recommended for immunocompetent patients with measles.Prevention of the spread of measles depends on prompt immunization of people at risk for exposure or people already exposed who cannot provide documentation of measles immunityRecommend supportive care with antipyretics, fluids, and rest.All of the above
21ManagementUncomplicated measles is self-limiting, lasting 10 to 12 days.Treatment in the majority of cases is supportive (antipyretics, fluids).Malnutrition, immunosuppression, poor health, and inadequate supportive care can worsen the prognosis in any patient. In developing nations, measles is a major cause of infant mortality.Vitamin A supplementation has shown to be of benefit in the treatment of measles.
22ComplicationsGroups at increased risk for complications of measles include immunocompromised hosts, pregnant women, malnourished individuals, and persons at extremes of ageMost common complications include otitis media, pneumonia, laryngotracheobronchitis (croup), and diarrhea. Hepatitis, thrombocytopenia, and encephalitis occur less commonly.Pneumonia is the most common fatal complication of measles in children and the most common complication overall in adults.
24Case Two: HistoryKylie Hinkle is 24-year-old woman who presents to your dermatology clinic with a red rash. She has been feeling unwell for the last 6 days with fever, myalgias, cough and sore throat. She also reports some tender lymph nodes on her neck. She has taken ibuprofen for the myalgias and fever, which has helped.A rash started on her face yesterday and is now spreading to her neck and trunk.
25Case Two: Skin ExamErythematous macules and papules on the face (not shown) and trunk (lesions are coalescing on the trunk)
26History ContinuedUpon further questioning you discover that Ms. Hinkle has never received the MMR (Measles, Mumps, Rubella) vaccine.
27Case Two, Question 1Based on the history and skin exam, what is the most likely diagnosis?Drug EruptionErythema InfectiosumMeaslesRoseolaRubella
28Case Two, Question 1 Answer: e Based on the history and skin exam, what is the most likely diagnosis?Drug Eruption (Less likely, but should get more information about NSAID use.)Erythema Infectiosum (More common in children. Eruption begins with bright red cheeks followed by a reticular eruption on the trunk and extremities.)Measles (Rash tends to spread over a period of days, not in 24 hours like this case.)Roseola (Occurs in young children with high fevers preceding a sudden rash that begins on the trunk.)Rubella
29Rubella Rubella is a viral disease Synonym: German measles, “3-day measles”Spread through direct or droplet contact from nasopharyngeal secretionsInfected individuals shed virus up to one week before and two weeks after onset of diseaseAppearance of the rash typically occurs days after exposure
30EpidemiologyOutbreaks occur most frequently in late winter and early springSchool-age children, adolescents, and young adults most often develop the diseaseThe incidence of rubella has dramatically decreased with routine vaccination
31Rubella: Clinical Presentation Many cases of non-congenital rubella are subclinicalProdrome: low-grade fever, headache, sore throat, conjunctivitis, rhinorrhea, cough and lymphadenopathy. Symptoms often resolve with appearance of the rash.Exanthem: pruritic, pink to red macules and papules which begin on face and spread to neck, trunk, and extremities over 24 hoursEnanthem: 20% with petechial lesions on soft palate and uvula (Forchheimer's sign)
32Clinical CourseAdults tend to have more prodromal symptoms and complications (although rare) compared to childrenArthritis sometimes accompanies exanthem (more common in teenagers and adult women)Rash begins to disappear in 2-3 days and clears the head and neck firstEncephalitis and thrombocytopenia are potential complicationsOther rare complications include: peripheral neuritis, optic neuritis, myocarditis, pericarditis, hepatitis, orchitis, and hemolytic anemia
33Case Two, Question 2Based on clinical presentation, you suspect rubella and recommend supportive treatment. What else would you like to know about Kylie?Any sick contactsHave you been in close contact with any pregnant women or immunocompromised individuals?What vaccines have you had?What was the date of your last period? Could you be pregnant?All of the above
34Case Two, Question 2 Answer: e What else would you like to know about Kylie?Any sick contacts (Identification of infected or exposed individuals will help control the potential outbreak)Have you been in close contact with any pregnant women or immunocompromised individuals? (Important to identify these at risk individuals)What vaccines have you had? (An important part of her health history)What was the date of your last period? (All women of child- bearing age with suspected rubella should be screened for pregnancy)All of the above
35Congenital Rubella Syndrome Infection during pregnancy may can result in miscarriage, fetal death, or cause congenital rubella syndrome which is associated with:Sensorineural deafnessMental retardationEye abnormalitiesCongenital heart diseaseCloudy Cornea
36Evaluation and Treatment Diagnosis is usually made using serology to detect rubella-specific IgM antibody or to document a 4-fold rise in antibody titer in acute and convalescent- phase serumAs with measles, rubella cases should be reported to local health departmentsTreatment consists of supportive careControl measures for rubella includes droplet precautions and exclusion from school or child care for seven days after the onset of the rash
38Case Three: HistoryKeith is an 10-year-old boy who was brought to the pediatrician by his mother because he developed low grade fevers, red cheeks and a new rash on his body.Keith is up to date with his vaccinations
39Case Three, Question 1How would you describe Keith’s rash?
40Case Three, Question 1Confluent, erythematous, edematous plaques on the malar eminences - “slapped cheeks.” Erythematous reticular eruption on the trunk and extremities
41Case Three, Question 2Based on the history and skin exam, what is the most likely diagnosis?Drug EruptionErythema InfectiosumMeaslesRoseolaRubella
42Case Three, Question 2 Answer: b Based on the history and skin exam, what is the most likely diagnosis?Drug Eruption (No exposure to medications)Erythema InfectiosumMeasles (Children with measles tend to appear more ill; Keith has been vaccinated)Roseola (Tends to occur in younger children with high fevers preceding a sudden rash that begins on the trunk)Rubella (Keith has been vaccinated; exanthem usually starts with erythematous macules and papules on the face)
43Parvovirus B19There are many clinical presentations associated with B19 infection (ranging from benign to life-threatening).Most infections are asymptomatic and unrecognizedWe will focus on Erythema Infectiosum, the most common clinical presentation.
44Diagnosis: Erythema Infectiosum Synonyms: Fifth diseaseCaused by Parvovirus B19Modes of transmission include contact with respiratory tract secretions, percutaneous exposure to blood or blood products, and vertical transmission from mother to fetusEstimated incubation period from exposure to onset of rash usually between 1-2 weeksIndividuals with erythema infectiosum are most infectious before onset of the rash
45EpidemiologyMost common in children 4-10 yrs old, but can affect all agesTends to occur in epidemics, especially associated with school outbreaks in the late winter and early springSecondary spread among susceptible household members is common, with infection occurring in ~ 50% of susceptible contactsSerologic studies show increasing prevalence of antibodies with ageIn most communities, ~ 50% of young adults and often more than 90% of elderly people are seropositive
46Erythema Infectiosum: Clinical Presentation Prodrome: low-grade fever, malaise, headache, pruritus, coryza, myalgias, joint pain (more common in adult women)Exanthem: Begins with bright red cheeks (“slapped cheeks”) and as the facial rash fades over 1-4 days, a symmetric, erythematous, reticular (lacelike) eruption appears on trunk and extremitiesEruption usually lasts 5-9 days
47DiagnosisDetection of serum parvovirus B19-specific IgM antibody is the preferred diagnostic testPositive IgM test result indicates that infection probably occurred within the previous 2 to 4 months
48Case Three, Question 3His mother states that his older brother has a rash mostly involving the hands and feet. Do you think he has parvovirus?No, because his older brother is likely already immune from previous exposureNo, because household transmission is rareNo, because the brother does not have a “slapped cheek” facial rashYes, he probably has papulopurpuric gloves-and-socks syndrome
49Case Three, Question 3 Answer: d His mother states that his older brother has a rash mostly involving the hands and feet. Do you think he has parvovirus?No, because his older brother is likely already immune from previous exposureNo, because household transmission is rareNo, because the brother does not have a “slapped cheek” facial rashYes, he probably has papulopurpuric gloves-and- socks syndrome
50Papular Purpuric Gloves and Socks Syndrome PPGSS presents as painful and pruritic papules, petechiae, and purpura of hands and feet, often with fever and enanthem (oral erosions).Unlike the typical rash of Erythema Infectiosum, patients with this presentation are viremic and contagious (they should not be around those at risk).
51Parvovirus B19: Special Considerations PregnancyInfection occurring during pregnancy can cause hydrops fetalis*, intrauterine growth retardation, pleural and pericardial effusions, and death. The risk of fetal death is between 2% and 6.5% when infection occurs during pregnancy.ImmunodeficiencyCan cause chronic erythroid hypoplasia with severe anemiaChronic hemolytic anemiasB19 is the most common cause of transient aplastic crisis in patients with chronic hemolytic anemias (i.e. sickle cell disease)*Hydrops fetalis: a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments
52TreatmentThere is no specific treatment for uncomplicated parvovirus B19 infectionSupportive therapy for relief of fatigue, malaise, pruritus, and arthralgia may be neededGenerally resolves after 5-10 days, but can reoccur for months upon exposure to sunlight, hot temperature, exercise, bathing, and stress
54Case Four: HistoryHPI: Caleb is a 9-month-old boy who presents for evaluation of fever and rash. His mother noted a fever of 40˚C two days ago. He appeared well and was eating and playing normally, so his mother was not alarmed. After the fever resolved, Caleb developed a red rash that progressed rapidly over the past 24 hours.
55Case Four, Question 1Based on Caleb’s history and exam, what is the most likely diagnosis?Drug EruptionErythema InfectiosumMeaslesRoseolaRubella
56Case Four, Question 1 Answer: d Based on Caleb’s history and exam, what is the most likely diagnosis?Drug EruptionErythema InfectiosumMeaslesRoseolaRubella
57Roseola Infantum Synonyms: Exanthema subitum, Sixth disease Caused by Human Herpesvirus 6 (HHV-6) and less commonly Human Herpesvirus 7 (HHV-7)Mode of transmission unknown (possibly from nasopharyngeal secretions)Children 6 months – 4 yearsMost common exanthem before age 2No vaccine; infection results in immunity
58HHV-6 HHV-6 infection in children results in: Subclinical infectionAcute febrile illness without rashExanthema subitumSeroprevalence of HHV-6 in the adult population is greater than 95%Reactivation in immunocompromised hosts may cause significant morbidityReactivation of HHV-6 with drug exposure can lead to drug-induced hypersensitivity syndrome (DIHS)
59Roseola Infantum: Clinical Presentation Infection with HHV-6 results in an acute febrile illness, lasting approximately 3 to 7 days, and can be followed by the characteristic rash of roseola (in ~ 20% of infected children)Prodrome: High fever (39-40°C), palpebral edema, cervical lymphadenopathy, mild upper respiratory symptoms. Child appears well. As fever subsides, exanthem appears (“exanthema subitum” means “sudden rash”).Exanthem: pink macules and papules surrounded by white halos. Begins on trunk, spreads to neck and proximal extremities.
60Prognosis and Treatment Usually benign and self-limitingHHV-6 is known to cause febrile seizure in children with infection, often without a rashTreatment may be necessary for atypical cases with complications and in immunosuppressed patients
61Take Home PointsExanthems are rashes that occur abruptly and affect multiple areas of the skin simultaneously.Morbilliform means “composed of erythematous macules and papules that resemble a measles rash.”Distinct viral exanthems are seen in measles, rubella, erythema infectiosum, and roseola infantum.Careful history taking and physical exam help establish the diagnosis.In the case of measles and rubella, clinical diagnosis should be serologically confirmed and reported.
62Classic Childhood Viral Exanthems NAMEEXANTHEM & ENANTHEMMeasles (Rubeola)Erythematous macules and papules begin on the face and spread cephalocaudally and centrifugally, Koplik spots.Rubella(German measles)Pruritic, pink to red macules and papules which begin on the face and spread to neck, trunk and extremities over 24hrs, Forchheimer’s sign.Erythema InfectiosumBegins with bright red cheeks and as the facial rash fades over 1-4 days, a symmetric, erythematous, reticular eruption appears on the trunk and extremities.Roseola Infantum (Exanthem subitum)Pink macules and papules surrounded by white halos. Begins on trunk, spreads to neck and proximal extremities.
63AcknowledgementsThis module was developed by the American Academy of Dermatology Medical Student Core Curriculum Workgroup fromPrimary authors: Laura S. Huff, MD; Cory A. Dunnick, MD, FAADContributor: Sarah D. Cipriano, MD, MPHPeer reviewers: Anna L. Bruckner, MD, FAAD; Brandon D. Newell, MD; Timothy G. Berger, MD, FAADRevisions and editing: Sarah D. Cipriano, MD, MPH, Jillian W. Wong. Last revised March 2011.
64ReferencesAmerican Academy of Pediatrics. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:[online]Barinaga J, Skolnik P. Epidemiology and transmission of measles. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2010.Barinaga J, Skolnik P. Clinical presentation and diagnosis of measles. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA,Bialecki C, Feder HM, Grant-Kels JM. The six classic childhood exanthems: A review and update. J Am Acad Dermatol. 1989; 21:
65ReferencesBelazarian Leah, Lorenzo Mayra E, Pace Nicole C, Sweeney Susan M, Wiss Karen M, "Chapter 192. Exanthematous Viral Diseases" (Chapter). Wolff K, Goldsmith LA, Katz SI, Gilchrest B, Paller AS, Leffell DJ: Fitzpatrick's Dermatology in General Medicine, 7e:Folster-Holst R, Kreth HW. Viral exanthems in childhood – infectious (direct) exanthems. Part 1: Classic exanthems. Journal of the German Society of Dermatology. 2009; 7:Jordan J. Clinical manifestations and pathogenesis of human parvovirus B19 infection. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2010.Scott LA, Stone MS. Viral exanthems. Dermatology Online Journal ; 9(3):4.