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Fifth and Sixth Diseases: More Than a Fever and a Rash

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Fifth and Sixth Diseases: More Than a Fever and a Rash Online excluSive Jason S. O’Grady, MD Department of Family Fifth and sixth diseases: Medicine, Mayo Clinic, More than a fever and a rash Rochester, Minn [email protected] The author reported no While most parvovirus B19 or HHV-6 infections resolve potential conflict of interest without sequelae, rheumatologic and hemolytic relevant to this article. complications and seizures can develop. ifth and sixth diseases are frequently encountered viral Practice exanthems in family medicine. This article delineates recommenDatiOnS the unique clinical characteristics of these disorders, › F Reserve serologic testing describes rare but serious sequelae of each, and offers recom- for parvovirus B19 for mendations to guide your practice. pregnant women with known exposure to the virus, immunocompromised Fifth disease individuals, or patients Parvovirus B19, an infectious agent found worldwide, is the with chronic hemolytic conditions or severe or cause of fifth disease, also known as slapped cheek syndrome persistent arthropathy B or erythema infectiosum. It is transmitted via respiratory drop- lets, most commonly in late winter and early spring. The peak › Keep in mind that incidence of parvovirus B19 infection is in children ages 5 to 15 up to 15% of children 1 infected with human years. Approximately 20% of parvovirus B19 infections remain 1,2 herpesvirus 6 can experience subclinical. An observational study of children in the United febrile seizures. Treat with Kingdom who were 6 months to 16 years of age and had been an antiepileptic drug, as you immunized for measles and rubella revealed that parvovirus would for any febrile seizure B19 was the number one identifiable cause of febrile rash, re- that lasts >5 minutes. C sponsible for 17% of cases.3 Seroprevalence increases with age, and 40% to 60% of adults test positive for prior infection.1 Strength of recommendation (SOr) A Good-quality patient-oriented evidence clinical presentation: B Inconsistent or limited-quality not necessarily limited to fever and rash patient-oriented evidence Parvovirus B19 has an incubation period of 4 to 21 days before C Consensus, usual practice, opinion, disease-oriented the classic symptoms of malaise, fever, and red “slapped” cheeks evidence, case series appear (FiGURE 1). Four to 14 days after the onset of symptoms, a pruritic lacy rash covers the entire body, preferentially on the ex- tensor surfaces (sparing the palms and soles), and may wax and wane for up to 3 weeks, with flaring triggered by stress, exercise, heat, or exposure to sunlight.1,4 Rarely, and usually among young adults, parvovirus B19 can cause papular-purpuric “gloves and stocking” syndrome, with fever, painful edema, erythema, and pruritus of the distal extremities.5 z associated arthritis. Parvovirus B19 may also cause a symmetric polyarthritis of the hands, wrists, knees, or ankles, jfponline.com Vol 63, no 10 | OCToBeR 2014 | The jouRnal of family PracTice e1 particularly in adult females. The course of FiGure 1 arthritis usually lasts 1 to 3 weeks, but up to Classic “slapped cheek” rash 20% may evolve into a chronic arthritis.6 In addition, numerous case studies suggest that of fifth disease parvovirus B19 may, in rare cases, cause a vi- ral myocarditis in infants and children.7 z Hemolytic complications. The target of parvovirus B19 is the erythroid blood cell line.1 Consequently, immunocompromised patients and those with chronic hemolytic conditions (eg, sickle cell disease, thalassemia, spherocytosis, or pyruvate kinase deficiency) may develop hematologic complications such as aplastic crisis, chronic anemia, thrombo- D cytopenia, neutropenia, or pancytopenia. Pa- m , INE tients with hemolytic complications can be T a S u quite ill, presenting with fever, malaise, tachy- . p cardia, tachypnea, and profound anemia. RD z Perinatal perils. Approximately one-third ICHA Parvovirus B19 of pregnant mothers are at risk for parvovirus of: R y S may cause B19 infection, and having children at home, e RT a severe medical condition, or stressful em- a symmetric COU polyarthritis, ployment have been shown to increase their particularly in risk of active infection.8 The annual incidence image The onset of this rash occurs at the end of the adult females, of symptomatic parvovirus B19 during preg- prodromal period and signals that the child is no usually lasting nancy is 1.5%, increasing to 13% during epi- longer infectious. one to 3 weeks. demics.9 Such infection can cause significant But it can evolve morbidity and mortality for the fetus. Moth- cated. However, consider serologic testing into a chronic ers newly infected during the first trimester for pregnant women with known exposure arthritis. have experienced a 71% increased risk of in- to the virus, immunocompromised patients, trauterine fetal demise (fetal loss <20 weeks patients with chronic hemolytic conditions, gestation) when compared with baseline risk or patients with severe or persistent arthrop- of fetal loss.9 In one prospective observation- athy. Serum immunoglobulin M can usually al study, fetal death was only observed when be detected 10 days after infection and can mothers were infected prior to 20 weeks of persist for 3 months, while serum immuno- gestation.10 Intrauterine B19 infection dur- globulin G is produced 2 weeks after inocula- ing any trimester carries a 4% overall risk of tion and presumably lasts for life.11 hydrops fetalis, thought to be due to high output cardiac failure secondary to severe treat supportively anemia.10 No specific treatment exists for parvovirus B19 infection. Management is supportive and rely on clinical findings to diagnose; the infection is usually mild and self-limiting. restrict serologic testing A nonsteroidal anti-inflammatory agent may The characteristic “slapped cheek” rash usu- be sufficient for associated arthritis; if need- ally distinguishes fifth disease from other ed, a low-dose oral corticosteroid can be used causes of febrile rash. Differential diagnosis without prolonging the viral illness.6 Refer for includes measles, scarlet fever, roseola in- hematologic consultation any immunocom- fantum, enterovirus, and adenovirus. A diag- promised patient with confirmed parvovirus nostic tool (TABLE) can help differentiate fifth who develops a hematologic complication, disease from other viral exanthems. which may require intravenous immuno- In most cases of suspected parvovirus globulin treatment or, in severe cases, bone B19 infection, serologic testing is not indi- marrow transplantation. e2 The jouRnal of family PracTice | OCToBeR 2014 | Vol 63, no 10 FIFTH AND SIXTH DISEASES TABLE Diagnostic aid for distinguishing among pediatric exanthems first disease Second disease Third disease fifth disease Sixth disease (rubeola) (scarlet fever) (german measles) (erythema (roseola infantum) infectiosum) causative agent measles virus pyrogenic exotoxin- Rubella virus parvovirus B19 human herpesvirus 6 producing group a (HHV-6) Streptococcus Mode of Respiratory Respiratory Respiratory Respiratory Saliva via mucosal transmission droplets droplets droplets droplets surfaces incubation period 8-12 days 2-5 days 14-21 days 4-21 days 10-15 days Symptoms fever, sore throat, red eyes, headache, 1st stage mild fever, fever, sore throat malaise, fever, red mild rhinorrhea, sore malaise, coalescing conjunctivitis, “slapped” cheeks throat, conjunctival pink macules cough, coryza, redness, high fever starting on the Koplik spots head and neck and spreading to the trunk and 2nd stage Red maculopapular fine, papular pruritic lacy body after fever abates, extremities, rash beginning on erythematous rash that spares tiny erythematous forchheimer the forehead and eruption around the palms and papules develop spots, petechial neck, spreading the neck, trunk, soles on the trunk and hemorrhage on soft to trunk, arms, and extremities spread to neck and palate and legs. (involves (face is usually extremities palms and soles spared), followed 50% of the time) by desquamation treatment Supportive antibiotics Supportive Supportive Supportive (penicillin or cephalosporins) Duration of illness 1st stage 2-4 days 1-2 days 3 days 4-14 days 3-5 days 2nd stage 7-10 days 3-4 days up to 3 weeks 1-3 days Sequelae Diarrhea, peritonsillar congenital polyarthritis, febrile seizures, encephalitis, abscess, otitis rubella syndrome, aplastic crisis, meningoencephalitis, pneumonia, otitis media, sinusitis, thrombocytopenia, chronic anemia, acute disseminated media, death pneumonia, arthritis, encephalitis pancytopenia, demyelination, rheumatic fever, intrauterine fetal hepatitis, myocarditis poststreptococcal demise, hydrops glomerulone- fetalis phritis, reactive arthritis vaccine preventable yes no yes no no clinical recommendations a child with erythema infectiosum is no lon- Parvovirus B19 is communicable only dur- ger infectious. At this stage, exclusion from ing the nonspecific prodromal period—the school or child care is unnecessary.1 4 to 21 days of incubation in which the pa- Perform serologic testing to determine tient seems to have a common cold, with immunity for all pregnant women with docu- coryza, sore throat, and headache. With the mented exposure to parvovirus B19.12 Retest appearance of the “slapped cheek” rash (an women who are initially nonimmune after 3 to immune-mediated, postinfectious sequela), 4 weeks. Patients who seroconvert should un- jfponline.com Vol 63, no 10 | OCToBeR 2014 | The jouRnal of family PracTice e3 FiGURE 2 junctival redness, followed by a high fever Sixth disease: The rash
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