Viral Exanthems

1. Viral Exanthems Medical Student Core Curriculum in Dermatology Last updated March 16, 2011

2. Goals and Objectives • The 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 exanthems • Describe classic presentations of distinctive pediatric viral exanthems • Provide counseling for parents of children with typical viral exanthems

3. Definitions • Exanthem (exanthema) • A rash that appears abruptly and affects several areas of the skin simultaneously • Greek origin “exanthema”which means “a breaking out” • Enanthem (enanthema) • An eruption upon a mucous membrane

4. Viral Exanthems • Commonly 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.

5. Morbilliform Rash Viral Exanthem Drug Rash

6. Classic Childhood Exanthems Historically, there were six childhood exanthems whose etiologies are now well-defined:

7. Case One Ana Haydon

8. Case One: History • Ana 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.

9. History Continued • Upon 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.

10. Case One: Skin Exam • Ana 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)

11. Exam Continued • Inspection of Ana’s mouth reveals, bluish-white dots on the mucosal surface. These are called Koplik spots.

12. Another Example of Koplik Spots

13. Case One, Question 1 • Based on the history and exam, what is the most likely diagnosis? • Drug Eruption • Erythema Infectiosum • Measles • Roseola • Rubella

14. Case 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) • Measles • Roseola (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)

15. Measles (Rubeola) Measles is a viral disease Spread by respiratory droplets Incubation period tends to be 8-12 days from exposure to onset of symptoms Patients are contagious from 1-2 days before onset of symptoms (3-5 days before the rash) to 4 days after appearance of the rash Immunocompromised patients can be contagious for the duration of the illness

16. Measles (Rubeola) Most common in children 3-5 years old Incidence of measles has decreased substantially where measles vaccination has been instituted Most cases of measles in the United States are imported with spread to unvaccinated individuals Measles 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)

17. Measles: Clinical Presentation Prodrome: Fever, Malaise, Conjunctivitis, Cough, Coryza*, Koplik spots Exanthem: 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

18. Diagnosis • Measles 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 RNA • Histologic evaluation of skin lesions or respiratory secretions may show syncytial keratinocytic giant cells

19. Case One, Question 2 • 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 immunity • Recommend supportive care with antipyretics, fluids, and rest. • All of the above

20. Case 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 immunity • Recommend supportive care with antipyretics, fluids, and rest. • All of the above

21. Management • Uncomplicated 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.

22. Complications • Groups at increased risk for complications of measles include immunocompromised hosts, pregnant women, malnourished individuals, and persons at extremes of age • Most 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.

23. Case Two Ms. Kylie Hinkle

24. Case Two: History • Kylie 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.

25. Case Two: Skin Exam • Erythematous macules and papules on the face (not shown) and trunk (lesions are coalescing on the trunk)

26. History Continued • Upon further questioning you discover that Ms. Hinkle has never received the MMR (Measles, Mumps, Rubella) vaccine.

27. Case Two, Question 1 • Based on the history and skin exam, what is the most likely diagnosis? • Drug Eruption • Erythema Infectiosum • Measles • Roseola • Rubella

28. Case 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

29. Rubella • Rubella is a viral disease • Synonym: German measles, “3-day measles” • Spread through direct or droplet contact from nasopharyngeal secretions • Infected individuals shed virus up to one week before and two weeks after onset of disease • Appearance of the rash typically occurs 14-17 days after exposure

30. Epidemiology • Outbreaks occur most frequently in late winter and early spring • School-age children, adolescents, and young adults most often develop the disease • The incidence of rubella has dramatically decreased with routine vaccination

31. Rubella: Clinical Presentation Many cases of non-congenital rubella are subclinical Prodrome: 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 hours Enanthem: 20% with petechial lesions on soft palate and uvula (Forchheimer's sign)

32. Clinical Course • Adults tend to have more prodromal symptoms and complications (although rare) compared to children • Arthritis sometimes accompanies exanthem (more common in teenagers and adult women) • Rash begins to disappear in 2-3 days and clears the head and neck first • Encephalitis and thrombocytopenia are potential complications • Other rare complications include: peripheral neuritis, optic neuritis, myocarditis, pericarditis, hepatitis, orchitis, and hemolytic anemia

33. Case Two, Question 2 • Based on clinical presentation, you suspect rubella and recommend supportive treatment. What else would you like to know about Kylie? • Any sick contacts • Have 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

34. Case 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

35. Congenital Rubella Syndrome • Infection during pregnancy may can result in miscarriage, fetal death, or cause congenital rubella syndrome which is associated with: • Sensorineural deafness • Mental retardation • Eye abnormalities • Congenital heart disease • Cloudy Cornea

36. Evaluation 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 serum • As with measles, rubella cases should be reported to local health departments • Treatment consists of supportive care • Control measures for rubella includes droplet precautions and exclusion from school or child care for seven days after the onset of the rash

37. Case Three Keith Walters

38. Case Three: History • Keith 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

39. Case Three, Question 1 How would you describe Keith’s rash?

40. Case Three, Question 1 Confluent, erythematous, edematous plaques on the malar eminences - “slapped cheeks.” Erythematous reticular eruption on the trunk and extremities

41. Case Three, Question 2 • Based on the history and skin exam, what is the most likely diagnosis? • Drug Eruption • Erythema Infectiosum • Measles • Roseola • Rubella

42. Case 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 Infectiosum • Measles (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)

43. Parvovirus B19 • There are many clinical presentations associated with B19 infection (ranging from benign to life-threatening). • Most infections are asymptomatic and unrecognized • We will focus on Erythema Infectiosum, the most common clinical presentation.

44. Diagnosis: Erythema Infectiosum • Synonyms: Fifth disease • Caused by Parvovirus B19 • Modes of transmission include contact with respiratory tract secretions, percutaneous exposure to blood or blood products, and vertical transmission from mother to fetus • Estimated incubation period from exposure to onset of rash usually between 1-2 weeks • Individuals with erythema infectiosum are most infectious before onset of the rash

45. Epidemiology • Most common in children 4-10 yrs old, but can affect all ages • Tends to occur in epidemics, especially associated with school outbreaks in the late winter and early spring • Secondary spread among susceptible household members is common, with infection occurring in ~ 50% of susceptible contacts • Serologic studies show increasing prevalence of antibodies with age • In most communities, ~ 50% of young adults and often more than 90% of elderly people are seropositive

46. Erythema 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 extremities Eruption usually lasts 5-9 days

47. Diagnosis • Detection of serum parvovirus B19-specific IgM antibody is the preferred diagnostic test • Positive IgM test result indicates that infection probably occurred within the previous 2 to 4 months

48. Case Three, Question 3 • 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 exposure • No, because household transmission is rare • No, because the brother does not have a “slapped cheek” facial rash • Yes, he probably has papulopurpuric gloves-and-socks syndrome

49. Case 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 exposure • No, because household transmission is rare • No, because the brother does not have a “slapped cheek” facial rash • Yes, he probably has papulopurpuric gloves-and-socks syndrome

50. Papular 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).