Module 1.2 - Macules and Papules
ERYTHEMA INFECTIOSUM AND PARVOVIRUS B19 INFECTION
5th Disease
Fitzpatrick’s Dermatology in General Medicine [9E]
AT-A-GLANCE ● Erythema infectiosum (Fifth disease): childhood illness with “slapped cheeks” followed by an erythematous,
lacy eruption on the trunk and extremities.
● Symmetric polyarthritis, particularly of the small joints in adults.
● Papular purpuric gloves-and-socks syndrome: pruritic erythema, edema, and petechiae of the hands and
feet, fever, and oral erosions in adolescents.
● Aplastic crisis in patients with increased red blood cell turnover, chronic anemia in immunocompromised
persons, and fetal hydrops
EPIDEMIOLOGY Worldwide Distribution: Erythema infectiosum is globally distributed and can affect individuals of all ages.
Seasonality and Epidemics: The disease can occur year-round but tends to appear in epidemics, particularly in
schools during late winter and early spring.
Seroprevalence:
● Antibodies against Parvovirus B19 increase with age.
● 15% to 60% of children aged 5 to 19 have antibodies.
● More than 90% of the elderly have antibodies.
Immunity: Previous infection with Parvovirus B19 typically provides lifelong immunity.
Incubation Period:
● The incubation period ranges from 4 to 14 days.
● During the viremia phase, which occurs 6 to 14 days after inoculation, patients may experience low-grade
fever and nonspecific symptoms.
● The characteristic rash typically appears around days 17 or 18.
Transmission:
● The primary mode of transmission is via the respiratory route through aerosolized droplets during the
viremic phase.
● After the rash appears, Parvovirus B19 is generally not detectable in respiratory secretions or serum,
indicating that individuals are infectious only before the rash develops.
● Close contact facilitates effective spread of the virus.
● The secondary attack rate among susceptible household contacts is approximately 50%.
Alternative Transmission Routes:
● Transmission can also occur via blood transfusion and blood products.
● Vertical transmission from mother to fetus is possible
ETIOLOGY AND PATHOGENESIS Virus Classification:
● Parvovirus B19 belongs to the family Parvoviridae and the genus Erythrovirus.
● It is a non-enveloped virus containing single-stranded DNA.
● B19 is the smallest known single-stranded DNA virus that infects humans, measuring 18 to 26 µm in
diameter.
Animal Parvoviruses:
, ● Parvoviruses are common in veterinary medicine, but there is no evidence that animal parvoviruses can be
transmitted to humans.
Infection Mechanism:
● Parvovirus B19 infects and lyses erythroid progenitor cells.
● The blood group P antigen (globoside) acts as a receptor for the virus.
● Individuals lacking the P antigen are not susceptible to B19 infection.
Serious Manifestations:
● In patients with increased red blood cell destruction or loss, who rely on compensatory increases in red cell
production, B19 infection can cause transient aplastic crisis.
● This includes patients with anemia due to acute or chronic blood loss.
Impact on Fetus:
● When B19 infects erythroblasts in a developing fetus with reduced red cell survival, it can lead to hemolysis
and anemia.
● This anemia may cause congestive heart failure, edema (fetal hydrops), and potentially fetal death.
Nonerythroid Tissue Involvement:
● Parvovirus B19 DNA can also be detected in nonerythroid tissues.
● The virus is associated with increased inflammatory gene expression in these tissues.
Immune Complex Deposition:
● Immune complex deposition has been implicated in some manifestations of B19 infection, including
erythema infectiosum.
CLINICAL FEATURES Parvovirus B19 infection in children:
● Asymptomatic Infections:
○ Most Parvovirus B19 infections in children are asymptomatic and go unrecognized.
● Fifth Disease:
○ Fifth disease is the most common clinical manifestation of Parvovirus B19.
○ It typically starts with nonspecific symptoms like headache, coryza (nasal congestion), and
low-grade fever approximately 2 days before the rash appears.
● Symptomatology:
○ Common symptoms that may coincide with the rash include:
■ Headache
■ Pharyngitis (sore throat)
■ Fever
■ Malaise
■ Myalgia (muscle pain)
■ Coryza
■ Diarrhea
■ Nausea
■ Cough
■ Conjunctivitis
○ Around 10% of children with erythema infectiosum develop arthralgia (joint pain) or arthritis, typically
affecting large joints more than small ones.
○ Occasionally, chronic joint complaints suggestive of juvenile idiopathic arthritis may occur.
, ● Characteristic Rash:
○ The rash begins with confluent, erythematous, and edematous plaques on the malar eminences,
often described as "slapped cheeks."
○ As the facial rash fades over 1 to 4 days, pink to erythematous macules or papules appear on the
trunk, neck, and extensor surfaces of the extremities.
○ These lesions may have central fading, giving them a lacy or reticulated appearance.
○ The rash can present in various forms, including morbilliform, confluent, circinate, or annular
patterns, with reports of palmar and plantar involvement.
○ The eruption typically lasts 5 to 9 days but can recur for weeks or months, triggered by factors such
as sunlight, exercise, temperature changes, bathing, and emotional stress.
○ In some outbreaks, pruritus (itching) is a prominent feature of the rash in children.
● Other Skin Manifestations:
○ There have been occasional reports of Parvovirus B19 associated with:
■ Generalized petechiae (small red or purple spots caused by bleeding)
■ Vascular purpura, including Henoch–Schönlein purpura
■ Microvesicular eruptions
● Enanthem:
○ An enanthem (rash on mucous membranes) may occur, characterized by erythema of the tongue
and pharynx, along with red macules on the buccal mucosa and palate.
Parvovirus B19 infection in adults:
● Primary Manifestation:
○ Acute arthropathy (joint disease) is the main manifestation in adults, especially in women.
○ It primarily affects the knees and small joints of the hands but can also involve the spine and
costochondral joints.
○ The arthritis is typically symmetric, of sudden onset, and self-limited, though it can persist or recur
for months.
○ It may mimic other conditions like Lyme arthritis or rheumatoid arthritis.
● Constitutional Symptoms:
○ Symptoms in adults are generally more severe than in children.
○ Common symptoms include fever, adenopathy (swollen lymph nodes), and mild arthritis without a
rash.
○ Women are more likely to experience joint complaints and rash, while men often present with only
flu-like symptoms.
○ Some adults may also experience fatigue, malaise, and depression lasting weeks after the infection.
● Asymptomatic Infection:
○ Asymptomatic infection can occur in adults, similar to children.
○ Numbness, tingling of the fingers, and pruritus (itching) have been reported with or without a rash.
● Rash in Adults:
○ If a rash is present in adults, it is usually macular, blotchy, or lacy, often appearing on the extremities
and rarely showing the characteristic slapped-cheek appearance.
○ Other cutaneous manifestations may include:
■ Purpura (small purple spots due to bleeding under the skin)
ERYTHEMA INFECTIOSUM AND PARVOVIRUS B19 INFECTION
5th Disease
Fitzpatrick’s Dermatology in General Medicine [9E]
AT-A-GLANCE ● Erythema infectiosum (Fifth disease): childhood illness with “slapped cheeks” followed by an erythematous,
lacy eruption on the trunk and extremities.
● Symmetric polyarthritis, particularly of the small joints in adults.
● Papular purpuric gloves-and-socks syndrome: pruritic erythema, edema, and petechiae of the hands and
feet, fever, and oral erosions in adolescents.
● Aplastic crisis in patients with increased red blood cell turnover, chronic anemia in immunocompromised
persons, and fetal hydrops
EPIDEMIOLOGY Worldwide Distribution: Erythema infectiosum is globally distributed and can affect individuals of all ages.
Seasonality and Epidemics: The disease can occur year-round but tends to appear in epidemics, particularly in
schools during late winter and early spring.
Seroprevalence:
● Antibodies against Parvovirus B19 increase with age.
● 15% to 60% of children aged 5 to 19 have antibodies.
● More than 90% of the elderly have antibodies.
Immunity: Previous infection with Parvovirus B19 typically provides lifelong immunity.
Incubation Period:
● The incubation period ranges from 4 to 14 days.
● During the viremia phase, which occurs 6 to 14 days after inoculation, patients may experience low-grade
fever and nonspecific symptoms.
● The characteristic rash typically appears around days 17 or 18.
Transmission:
● The primary mode of transmission is via the respiratory route through aerosolized droplets during the
viremic phase.
● After the rash appears, Parvovirus B19 is generally not detectable in respiratory secretions or serum,
indicating that individuals are infectious only before the rash develops.
● Close contact facilitates effective spread of the virus.
● The secondary attack rate among susceptible household contacts is approximately 50%.
Alternative Transmission Routes:
● Transmission can also occur via blood transfusion and blood products.
● Vertical transmission from mother to fetus is possible
ETIOLOGY AND PATHOGENESIS Virus Classification:
● Parvovirus B19 belongs to the family Parvoviridae and the genus Erythrovirus.
● It is a non-enveloped virus containing single-stranded DNA.
● B19 is the smallest known single-stranded DNA virus that infects humans, measuring 18 to 26 µm in
diameter.
Animal Parvoviruses:
, ● Parvoviruses are common in veterinary medicine, but there is no evidence that animal parvoviruses can be
transmitted to humans.
Infection Mechanism:
● Parvovirus B19 infects and lyses erythroid progenitor cells.
● The blood group P antigen (globoside) acts as a receptor for the virus.
● Individuals lacking the P antigen are not susceptible to B19 infection.
Serious Manifestations:
● In patients with increased red blood cell destruction or loss, who rely on compensatory increases in red cell
production, B19 infection can cause transient aplastic crisis.
● This includes patients with anemia due to acute or chronic blood loss.
Impact on Fetus:
● When B19 infects erythroblasts in a developing fetus with reduced red cell survival, it can lead to hemolysis
and anemia.
● This anemia may cause congestive heart failure, edema (fetal hydrops), and potentially fetal death.
Nonerythroid Tissue Involvement:
● Parvovirus B19 DNA can also be detected in nonerythroid tissues.
● The virus is associated with increased inflammatory gene expression in these tissues.
Immune Complex Deposition:
● Immune complex deposition has been implicated in some manifestations of B19 infection, including
erythema infectiosum.
CLINICAL FEATURES Parvovirus B19 infection in children:
● Asymptomatic Infections:
○ Most Parvovirus B19 infections in children are asymptomatic and go unrecognized.
● Fifth Disease:
○ Fifth disease is the most common clinical manifestation of Parvovirus B19.
○ It typically starts with nonspecific symptoms like headache, coryza (nasal congestion), and
low-grade fever approximately 2 days before the rash appears.
● Symptomatology:
○ Common symptoms that may coincide with the rash include:
■ Headache
■ Pharyngitis (sore throat)
■ Fever
■ Malaise
■ Myalgia (muscle pain)
■ Coryza
■ Diarrhea
■ Nausea
■ Cough
■ Conjunctivitis
○ Around 10% of children with erythema infectiosum develop arthralgia (joint pain) or arthritis, typically
affecting large joints more than small ones.
○ Occasionally, chronic joint complaints suggestive of juvenile idiopathic arthritis may occur.
, ● Characteristic Rash:
○ The rash begins with confluent, erythematous, and edematous plaques on the malar eminences,
often described as "slapped cheeks."
○ As the facial rash fades over 1 to 4 days, pink to erythematous macules or papules appear on the
trunk, neck, and extensor surfaces of the extremities.
○ These lesions may have central fading, giving them a lacy or reticulated appearance.
○ The rash can present in various forms, including morbilliform, confluent, circinate, or annular
patterns, with reports of palmar and plantar involvement.
○ The eruption typically lasts 5 to 9 days but can recur for weeks or months, triggered by factors such
as sunlight, exercise, temperature changes, bathing, and emotional stress.
○ In some outbreaks, pruritus (itching) is a prominent feature of the rash in children.
● Other Skin Manifestations:
○ There have been occasional reports of Parvovirus B19 associated with:
■ Generalized petechiae (small red or purple spots caused by bleeding)
■ Vascular purpura, including Henoch–Schönlein purpura
■ Microvesicular eruptions
● Enanthem:
○ An enanthem (rash on mucous membranes) may occur, characterized by erythema of the tongue
and pharynx, along with red macules on the buccal mucosa and palate.
Parvovirus B19 infection in adults:
● Primary Manifestation:
○ Acute arthropathy (joint disease) is the main manifestation in adults, especially in women.
○ It primarily affects the knees and small joints of the hands but can also involve the spine and
costochondral joints.
○ The arthritis is typically symmetric, of sudden onset, and self-limited, though it can persist or recur
for months.
○ It may mimic other conditions like Lyme arthritis or rheumatoid arthritis.
● Constitutional Symptoms:
○ Symptoms in adults are generally more severe than in children.
○ Common symptoms include fever, adenopathy (swollen lymph nodes), and mild arthritis without a
rash.
○ Women are more likely to experience joint complaints and rash, while men often present with only
flu-like symptoms.
○ Some adults may also experience fatigue, malaise, and depression lasting weeks after the infection.
● Asymptomatic Infection:
○ Asymptomatic infection can occur in adults, similar to children.
○ Numbness, tingling of the fingers, and pruritus (itching) have been reported with or without a rash.
● Rash in Adults:
○ If a rash is present in adults, it is usually macular, blotchy, or lacy, often appearing on the extremities
and rarely showing the characteristic slapped-cheek appearance.
○ Other cutaneous manifestations may include:
■ Purpura (small purple spots due to bleeding under the skin)
