Page 1

Fifth disease 

Updated 2013 Jan 16 10:07:00 AM: case report of acute glomerulonephritis in an immunocompetent elderly woman after contact with child who had been diagnosed as erythema infectiosum (Intern Med 2012) view updateShow more updates

Related Summaries:  

Parvovirus B19 arthropathy Parvovirus B19 infection (congenital)

General Information Description:  

benign self-limited infectious disease caused by parvovirus B19, common in childhood and usually identified by characteristic "slapped cheek" rash (1, 2, 3) the term "fifth disease" refers to its having been the fifth of 6 erythematous childhood exanthems which were described in the following order o measles (rubeola), 1627 o scarlet fever, 1627 o rubella (German measles), 1881 o Filatow-Dukes' disease, 1900 (existence controversial, possibly attributable to staphylococcal scalded skin syndrome) o erythema infectiosum, 1905 o roseola infantum (exanthem subitum), 1910 o Reference - Lancet 2001 Jan 27;357(9252):299, commentary can be found in Lancet 2001 Jun 23;357(9273):2059

Also called:  

erythema infectiosum (EI) slapped cheek disease

Organs involved:  

skin may involve joints

Who is most affected: 

children, peak incidence between ages 6-14 years(2)


more common in late winter and early spring(1, 2, 3)

Incidence/Prevalence: 

parvovirus B19 infection occurs worldwide, both sporadically and in epidemics (1, 2, 3)

antiparvovirus antibodies are present in > 60% of adults and in 50% of children by age 15 years(2, 3)

Causes and Risk Factors Causes: 

human parvovirus B19 (HPV B19), a member of Parvoviridae family(2, 3) o single-stranded DNA virus o only member of Parvoviridae family that causes disease in humans o identified in 1975 and linked to fifth disease in 1983

Pathogenesis: 

infection(1, 2, 3) o virus targets erythroid progenitor cells (found in human bone marrow, peripheral blood, fetal liver, and umbilical cord) o infects by attaching to P blood group antigen cellular receptor o most symptoms are due to immune complex formation and deposition (usually in skin or joints) o usual incubation period is about 4-14 days, but may last up to 21 days before prodromal symptoms appear transmission(1, 2, 3) o respiratory spread is most common route o transplacental, nosocomial, and blood product transmission less common o transmission occurs during week prior to onset of rash (viremic phase), disease is no longer contagious once rash appears o transmission rates  about 50% for household contacts  10%-60% for school and daycare contacts o transmission may also occur with bone marrow or organ transplant (BJOG 2011 Jan;118(2):175 ) immunity(3) o immunoglobulin G (IgG) antibodies produced during initial infection in immunocompetent patients confer future immunity to parvovirus B19 o inability to produce adequate antibody response may result in persistent or recurrent parvovirus infection

Likely risk factors:


  

close contact with infected person during week prior to onset of rash(1, 2) defective immunoglobulin production(3) exposure to virus through transfusion, hospitalization, or maternal-fetal transfer(1, 2, 3)

presence of P antigen on erythrocytes (erythrocytes in persons with rare P phenotype blood group lack P antigen and cannot be infected with parvovirus B19)(3) immunocompromised patients and patients with decreased erythrocytes (due to iron deficiency anemia, HIV infection, sickle cell disease) have higher risk of aplastic crisis or chronic red cell aplasia (Am Fam Physician 2007 Feb 1;75(3):373 )

Complications and Associated Conditions Complications: 

general complications(1, 2, 3) o arthropathy (may be a complication of fifth disease, but can also occur with parvovirus infection that does not manifest as fifth disease) occurs in  about 8% of children  up to 60% of adolescents and adults (2 times more common in women)  caused by antigen-antibody complex deposition o transient aplastic crisis  may occur in disorders with decreased number of erythrocytes such as  iron deficiency anemia in adults or children  HIV infection  sickle cell disease  hereditary spherocytosis  thalassemia  may cause  heart failure  cerebrovascular accident  acute splenic sequestration o gloves and socks syndrome (painful symmetric erythema and edema of hands and feet, which progresses to petechiae and purpura, and sometimes to vesicles, bullae, and skin sloughing) pregnancy complications with maternal parvovirus B19 infection (including but not limited to fifth disease) o transplacental infection of fetus (30% estimated risk) o fetal loss (5%-10% estimated risk) o hydrops fetalis, especially with maternal infection during second trimester o Reference - BJOG 2011 Jan;118(2):175

History and Physical History:


Chief concern (CC): 

rash(1, 2, 3) o "slapped cheek" facial rash is common presentation in children, may be less noticeable in adults o rash evolves to include a lacy body rash which may fade and recur over several weeks

History of present illness (HPI): 

ask about(1, 2) o symptoms present before onset of rash, mild 3-7 day prodrome common and may include  fever  coryza  headache  nausea  malaise  sore throat o rash, which usually develops in 3 overlapping stages and may be pruritic  first stage - "slapped cheek" facial rash lasting 2-4 days, may worsen with sun exposure  second stage - reticular, lacy pattern body rash lasting 1-6 weeks  third stage - rash repeatedly fades and reappears (often in relation to heat or sunlight) for 1-3 weeks o joint symptoms (arthralgia or arthritis) - parvovirus B19 infection associated with arthralgia in about 8% of children and up to 60% of adolescents and adults, especially women ask about pregnancy because transplacental transmission can occur (1)

Past medical history (PMH): 

ask about recent hospitalization or transfusion, because nosocomial and blood product transmission can occur(1, 2, 3)

Social history (SH): 

ask about illness among recent contacts(1) o about 50% transmission rate for household contacts o 10%-60% transmission with school or daycare exposure to parvovirus B19

Physical: General physical: 

general lymphadenopathy may be present (JAAPA 2009 Jun;22(6):42 PDF)


Skin: 

 

rash which changes in appearance during 3 overlapping stages of illness (1, 2) o first stage - intensely erythematous facial rash (may not occur in all patients with fifth disease, more common in children than adults)  red papules develop on both cheeks and coalesce rapidly to form symmetrical, warm, slightly edematous plaques  nasal bridge and perioral region usually spared, resulting in characteristic "slapped cheek" appearance  rash may be exacerbated by sun exposure  usually fades in 2-4 days o second stage - erythematous body rash  generally appears 1-4 days after onset of facial rash, but may appear without preceding rash  maculopapular rash develops over trunk, buttocks, and extremities  central clearing of rash results in characteristic reticular, lacy pattern  reticular rash usually spreads dorsoventrally and is most prominent on proximal extremities  usually fades in 1-2 weeks, may last up to 6 weeks o third stage - fluctuating rash  rash fades and reappears on previously affected sites  fluctuations may be related to sun exposure, heat, or emotional upset  usually resolves completely and without scarring in 1-3 weeks excoriations may be present because rash can be pruritic (2) review of fifth disease, including image of typical rash appearance, can be found in Can Fam Physician 2009 Dec;55(12):1195

HEENT: 

circumoral pallor during first stage of rash(1)

Cardiac: 

assess for heart failure in patients at risk for transient aplastic crisis due to diseases associated with low baseline number of red blood cells(1)

Abdomen: 

assess for splenomegaly due to acute sequestration in patients at risk for transient aplastic crisis due to diseases associated with low baseline number of red blood cells(1)

Extremities: 

assess joints for arthropathy (2) o evaluate for signs of arthritis (1) o usual distribution in fifth disease


in children often involves knees (82% of patients) or ankles and may be symmetric or asymmetric  in adults  symmetric and polyarticular  proximal interphalangeal and metacarpophalangeal joint involvement common  knee, wrist, and ankle involvement less common assess hands and feet for gloves and socks syndrome (symmetric erythema and edema which progresses to petechiae and purpura, and sometimes to vesicles, bullae, and skin sloughing)(1, 2, 3)

Neuro: 

assess for findings suggestive of cerebrovascular accident in patients at risk for transient aplastic crisis due to diseases associated with low baseline number of red blood cells(1)

Diagnosis Making the diagnosis:  

diagnosis usually based on presence of characteristic rash (1, 2) laboratory confirmation of parvovirus B19 infection usually reserved for pregnant women and patients without typical rash(1)

Rule out: 

other causes of similar-appearing erythematous rashes important to consider, including(2) o viral exanthems caused by  rubella (German measles)  measles (rubeola)  roseola infantum  enteroviruses o rashes caused by bacterial infections  scarlet fever  erysipelas o erythema due to  drug reaction  allergic contact dermatitis or other allergic response  sunburn  collagen vascular disease

Testing overview: 

testing not needed in most patients presenting with characteristic rash (1, 2)


blood tests for patients requiring laboratory confirmation of infection or without typical rash o parvovirus B19-specific serum testing  immunoglobulin M (IgM)  identifies recent infection in immunocompetent patient  may be undetectable in immunocompromised patient or at onset of transient aplastic crisis  immunoglobulin G (IgG)  identifies recent or prior infection (other testing needed to determine when infection occurred)  confers lifelong immunity to parvovirus  viral DNA (polymerase chain reaction [PCR] testing preferred)  identifies current viremia due to recent or persistent infection  may be useful to identify disease in patient unable to mount normal immunoglobulin M (IgM) or immunoglobulin G (IgG) response  indicates patient is contagious  testing children for IgM antibodies plus viral DNA might identify acute parvovirus B19 infection missed by either test alone (level 2 [mid-level] evidence) o complete blood count with differential and smear to help identify complications of parvovirus B19 infection such as transient aplastic crisis and fetal anemia testing in pregnant women with possible parvovirus B19 infection o serum IgG and IgM o consider PCR for viral DNA if IgM is negative o IgM testing alone or DNA testing alone may miss 4%-6% of parvovirus B19 infections in pregnant women (level 2 [mid-level] evidence) o weekly fetal ultrasound monitoring for confirmed parvovirus B19 infection

Blood tests: 

serum parvovirus B19-specific tests(1, 2, 3) o immunoglobulin M (IgM) antibodies  produced 10-12 days after infection in immunocompetent patient (Clin Microbiol Rev 2002 Jul;15(3):485 )  persists 2-3 months and indicates parvovirus B19 infection occurred within that time period  not present at onset of transient aplastic crisis, and may not be detected in immunocompromised patients o immunoglobulin G (IgG) antibodies  may be detected about 2 weeks after infection in immunocompetent patient and persist indefinitely (which provides lifelong immunity) (Clin Microbiol Rev 2002 Jul;15(3):485 )  new presence confirms recent infection (requires serum sample obtained prior to illness or early in disease course to compare with later sample)


if prior serum sample not available for comparison, IgG antibodies only indicates previous infection and immunity (but cannot confirm parvovirus B19 as cause of recent illness)  not present during transient aplastic crisis, and may not be detected in immunocompromised patients o viral DNA testing  useful to detect parvovirus B19 infection in patients with abnormal antibody production resulting in absence of detectable IgM and IgG levels  in transient aplastic crisis  viremia persists (and patient is highly contagious) until antibodies are produced and clear the infection  IgM antibodies usually appear a few days after onset of transient aplastic crisis, but may not be detectable in early testing o polymerase chain reaction (PCR) testing preferred over less sensitive nucleic acid hybridization assays o testing children for IgM antibodies plus viral DNA might identify acute parvovirus B19 infection missed by either test alone (level 2 [mid-level] evidence)  based on diagnostic cohort study with all tests not applied to all patients  167 children aged 6 months to 17 years hospitalized for acute illness potentially attributable to human parvovirus B19 infection had serum tested at admission for parvovirus B19 DNA (by PCR) and/or IgM (by enzyme-linked immunosorbent assay [ELISA])  inclusion criteria were ≥ 1 of  acute nonallergic exanthem  fever for > 1 week  aplastic anemia or pancytopenia  acute nonbacterial arthropathy  immune thrombocytopenia (ITP)  Henoch-Schonlein purpura (HSP)  aseptic meningitis  acute parvovirus B19 infection (defined as positive serum B19 DNA and/or B19 IgM, negative serum B19 IgG, and no other proven infection) diagnosed in 21 children (12.6%), of whom 19 were tested for both B19 DNA and B19 IgM  both studies were positive in 10 children (53%)  DNA test only was positive in 7 children (37%)  IgM test only was positive in 2 children (11%)  no acute parvovirus infection detected in 15 children with immune thrombocytopenic purpura (ITP), 9 children with Henoch-Schönlein purpura (HSP), 6 children with aseptic meningitis, and 70 controls with proven non-B19 infection  Reference - Pediatr Infect Dis J 2006 Oct;25(10):898 complete blood count with differential and smear


o

common findings include  decreased reticulocyte count and hemoglobin concentration 1-2 weeks after infection, which return to normal within 1 month (JAAPA 2009 Jun;22(6):42 PDF) (1)  giant pronormoblasts on peripheral blood smear (3) o findings in patients with complications may include  anemia, decreased white blood cell count, thrombocytopenia, and pancytopenia in transient aplastic crisis  severe anemia and thrombocytopenia in hydrops fetalis testing in pregnant women with fifth disease, suspicion of parvovirus B19 infection, contact with fifth disease-infected person, or other parvovirus B19 exposure should include o maternal serum for parvovirus B19-specific IgM and IgG to determine whether recent infection occurred  if both IgG and IgM are positive OR IgG is negative and IgM is positive, mother has current active infection and fetal ultrasound indicated  if IgG positive and IgM negative  mother probably has immunity from prior infection (no recent infection)  consider PCR testing for viral DNA because IgM testing has decreasing sensitivity as IgM clears  if PCR negative - mother has past immunity, no active infection, and needs no further testing  if PCR positive - mother has current active infection (perform fetal ultrasound)  if both IgG and IgM negative  mother has no current active infection (and is not immune to parvovirus B19)  consider PCR testing for viral DNA  retest for IgG and IgM in 14 days  if follow-up tests remain negative, no further testing needed (see above for any positive test results)  Reference - Prenat Diagn 2011 May;31(5):419 o IgM testing alone or DNA testing alone may miss 4%-6% of parvovirus B19 infections in pregnant women (level 2 [mid-level] evidence)  based on retrospective cohort study with all tests not applied to all patients  72 pregnant women with confirmed parvovirus B19 infection (defined as maternal serum positive for B19-specific IgM and/or DNA) were assessed for test positivity  IgM was positive in 64 (94%) of 68 women tested  DNA was positive in 26 (96%) of 27 women tested  Reference - J Clin Microbiol 2011 Oct;49(10):3514 o see also Parvovirus B19 infection (congenital)

Imaging studies:


ultrasound o perform weekly fetal ultrasound to detect hydrops fetalis and fetal anemia in pregnant women with confirmed parvovirus B19 infection  findings in hydrops fetalis (in addition to fluid accumulation in ≥ 2 fetal body compartments) may include  ascites  enlargement and thickening of heart or pericardial effusion  skin edema  placental edema  normal or decreased amniotic fluid  findings with fetal anemia may include increased peak blood flow velocity (as indicator of increased cardiac output) on Doppler ultrasound of middle cerebral artery o refer to fetal medicine specialist for signs of anemia or hydrops fetalis o discontinue weekly ultrasound if negative for 20 weeks after exposure o Reference - Prenat Diagn 2011 May;31(5):419 o see also Parvovirus B19 infection (congenital)

Biopsy and pathology: 

bone marrow biopsy in patients with transient aplastic crisis shows absence of maturing erythroid precursors and giant pronormoblasts(3)

Treatment Treatment overview: 

 

disease is self-limited, so usual management is home care with symptomatic treatment only(1, 2, 3) o analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) for arthralgia o antihistamines or topical antipruritics for pruritus o school exclusion not necessary because patient is no longer contagious once rash appears admission may be indicated for some complications, such as transient aplastic crisis or hydrops fetalis(3) inpatient management o use infection control procedures to avoid transmission of parvovirus B19 to susceptible patients or healthcare workers from patients admitted with aplastic crisis (3) o blood transfusion for significant anemia refer pregnant women with confirmed parvovirus B19 infection to fetal medicine specialist (Prenat Diagn 2011 May;31(5):419)

Prognosis 

self-limited disease in most patients(1, 2, 3)


 

usually resolves without permanent sequelae in < 6 weeks(1, 2) patients able to produce immunoglobulin G (IgG) antibodies to parvovirus B19 (immunocompetent patients) have lifetime immunity and are not susceptible to reinfection(3) prognosis in patients with complications of fifth disease or other parvovirus B19associated condition (1) o arthropathy  usually resolves within 3 weeks, but may persist for years (prolonged course more common in women)  no articular erosion occurs (1, 3) o transient aplastic crisis  self-limited, usually resolves within 2 weeks  anemia may become severe and result in heart failure, cerebrovascular accident, or acute splenic sequestration (1) o gloves and socks syndrome usually resolves in 1-3 weeks without scarring prognosis in pregnant women with fifth disease or other parvovirus B19 infection o maternal infection associated with estimated 30% risk of transplacental transmission(1, 3) o pregnancy complication rate is about 3%, including  miscarriage  may occur in up to 10% infected during first trimester  greatest risk is at 9-16 weeks gestation  severe fetal anemia  nonimmune hydrops fetalis  usually occurs 2-4 weeks after maternal infection  clinical signs usually present at 22-23 gestational weeks  may be caused by  severe anemia with heart failure (greatest risk at 8-20 gestational weeks)  viral myocarditis with heart failure  hepatitis-related hypoalbuminemia  intrauterine fetal demise  Reference - Can Fam Physician 2009 Dec;55(12):1195  delayed psychomotor development in 32% of survivors after fetal transfusion for hydrops associated with parvovirus B19 infection  based on retrospective cohort study of 24 hydropic fetuses with congenital parvovirus B19 infection having intrauterine transfusions  congenital parvovirus B19 infection confirmed by presence of parvovirus B19-specific immunoglobulin M or parvovirus B19 DNA in fetal blood samples  follow-up in 16 surviving fetuses at age 6 months to 8 years  11 (68%) were normal  5 (32%) had delayed psychomotor development  Reference - Obstet Gynecol 2007 Jan;109(1):42


o

o

o

maternal parvovirus B19 infection associated with about 6% fetal mortality but risk appears very low if infected after 20 gestational weeks  based on prospective cohort study  1,018 pregnant women with serologically confirmed acute parvovirus B19 infection were assessed  gestational outcomes included  fetal death in 64 (6.3%), all occurring in mothers infected at < 20 gestational weeks  hydrops fetalis in 40 fetuses (3.9%), including 23 with severe hydrops (2.3% of total cohort)  survival in 11 of 13 fetuses (85%) transfused in utero for severe hydrops fetalis vs. 0% of 10 fetuses not transfused for severe hydrops  Reference - Prenat Diagn 2004 Jul;24(7):513 maternal parvovirus B19 infection at < 20 gestational weeks appears to increase risk of vertical transmission, hydrops fetalis, and fetal loss  based on cohort study  59 (82%) of 72 pregnant women with confirmed parvovirus B19 infection (defined as maternal serum positive for B19-specific immunoglobulin M [IgM] and/or DNA) had virologic and clinical follow-up of their fetuses or neonates  vertical transmission occurred in 39% (23 pregnancies) and was associated with  documented maternal infection during  first trimester in 8 pregnancies (35%)  second trimester and before 20 gestational weeks in 8 pregnancies (35%)  second trimester and after 20 gestational weeks in 3 pregnancies (13%)  third trimester in 4 pregnancies (17%)  nonimmune hydrops fetalis in 11.9% (7 fetuses, all B19 positive)  fetal loss in 86% (6 pregnancies)  2 miscarriages and 2 intrauterine fetal demises, all with maternal infection before 20 gestational weeks  2 voluntary terminations  survival with normal neurodevelopmental outcome in 1 infant  live birth in 17 infants (74%)  Reference - J Clin Microbiol 2011 Oct;49(10):3514 see also Parvovirus B19 infection (congenital)

Prevention and Screening Prevention:


to avoid transmission to susceptible patients or healthcare workers from patients admitted with aplastic crisis or chronic parvovirus B19 infection (1) o isolation o droplet precautions for 7 days (or duration of hospitalization in immunocompromised patients with chronic infection)  healthcare workers or close contacts should wear mask (respirator not necessary) when entering patient's room  patient should wear mask when transported outside of room  Reference - Centers for Disease Control and Prevention (CDC) guideline for isolation precautions (CDC 2007 PDF) o pregnant healthcare workers advised not to participate in care of these patients (AAOHN J 2008 Aug;56(8):329) school exclusion ineffective because disease is no longer contagious once erythema infectiosum appears(2)

Screening: 

routine screening of pregnant women for parvovirus not indicated(1)

Guidelines and Resources Guidelines: 

American College of Obstetricians and Gynecologists (ACOG) practice bulletin on perinatal viral and parasitic infections can be found in Int J Gynaecol Obstet 2002 Jan;76(1):95 (reaffirmed 2009 Dec) Public Health Laboratory Service (PHLS) guideline on management of, and exposure to, rash illness in pregnancy (including consideration of relevant antibody screening programmes in pregnancy) can be found in Commun Dis Public Health 2002 Mar;5(1):59 Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline on parvovirus B19 infection in pregnancy can be found in J Obstet Gynaecol Can 2002 Sep;24(9):727

Review articles:      

review of erythema infectiosum can be found in JAAPA 2009 Jun;22(6):42 PDF review of parvovirus B19 infection can be found in CMAJ 2005 Mar 15;172(6):743 review of parvovirus B19 infection in pregnancy can be found in Prenat Diagn 2011 May;31(5):419 review of parvovirus B19 infection in pregnancy can be found in BJOG 2011 Jan;118(2):175 review of generalized rash (differential diagnosis) can be found in Am Fam Physician 2010 Mar 15;81(6):726 review of generalized rash (diagnostic approach) can be found in Am Fam Physician 2010 Mar 15;81(6):735


ď&#x201A;ˇ

case report of acute glomerulonephritis in an immunocompetent elderly woman after contact with child who had been diagnosed as erythema infectiosum can be found in Intern Med 2012;51(16):2197

Fifth disease  
Read more
Read more
Similar to
Popular now
Just for you