21 Nov 2013 Danize Buemio Mary April Chan

21 Nov 2013 Danize Buemio Mary April Chan
VIRAL EXANTHEMS 21 Nov 2013 Danize Buemio Mary April Chan

MEASLES

Measles Etiology Measles virus
Single-stranded lipid enveloped RNA virus Family Paramyxoviridae, genus Morbilivirus 6 major structural proteins Hemagglutinin (H) protein Fusion (F) protein – antibodies limit proliferation

Measles Transmission Contact with large droplets or small droplet aerosols in which virus is suspended Entry into respiratory tract or conjunctivae Approx. 90% of exposed individuals develop measles Face-fece contact is not necessary Viable virus may be suspended in the air up to 1 hour

Measles Pathology Necrosis of the respiratory tract epithelium with lymphocytic infiltrate Small vessel vasculitis on the skin and oral mucosa Histological findings Rash reveals intracellular edema and dyskeratosis Epidermal syncytial giant cells with up to 26 nuclei Lymphoid hyperplasia Fusion of infected cells  multinucleated giant cells Warthin-Finkeldey giant cells: pathognomonic for measles, up to 100 nuclei Warthin-Finkeldey cell from lung tissue.

Measles Incubation Period Prodromal Illness Exanthematous Phase
Recovery

Measles Incubation period: 8-12 days
Prodromal Illness Exanthematous Phase Recovery Incubation period: 8-12 days Virus migrates to regional lymph nodes Primary viremia disseminates the virus to the reticuloendothelial system Secondary viremia spreads virus to body surfaces

Measles Incubation Period Prodromal Illness Exanthematous Phase Recovery Prodromal Phase: mild fever, Conjunctivitis with photophobia, Coryza, Cough Enanthem: Koplik spots  pathognomonic Appears 1-4 days before rash Symptoms increase in intensity for 2-4 days until 1st day of the rash Epithelial necrosis Giant cell formation Viral shedding Viral replication The enanthem, Koplik spots, is the pathognomonic sign of measles and appears 1 to 4 days prior to the onset of the rash They first appear as discrete red lesions with bluish white spots in the center on the inner aspects of the cheeks at the level of the premolars. They may spread to involve the lips, hard palate, and gingiva. They also may occur in conjunctival folds and in the vaginal mucosa. Koplik spots have been reported in 50–70% of measles cases but probably occur in the great majority.

Measles Incubation Period Prodromal Illness Exanthematous Phase Recovery Exanthem: maculopapular rash begins around forehead (hairline), behind the ears, upper neck  torso  extremities Antibody production  viral replication and symptoms subside, rash fades over 7 days  desquamation Infection of CD4 T cells  suppresion of immune response Of the major symptoms of measles, the cough lasts the longest, often up to 10 days. In more severe cases, generalized lymphadenopathy may be present, with cervical and occipital lymph nodes especially prominent.

Inapparent Measles Infection
Subclinical form of measles Individuals with passively acquired antibody Infants, recepients of blood products Rash may be indistinct, brief or absent Do not shed measles virus or transmit infection

Atypical measles Original formalin-inactivated measles vaccine
More severe form High onset of fever and headache Maculopapular rash on the extremities  petechial and purpuric Progress in centripetal direction Frequently complicated by pneumonia and pleural effusion Circulating immune complexes due to abnormal response to vaccine

Diagnostics CBC Serologic confirmation: IgM and IgG
Reduction in WBC count Decrease in lymphocytes > neutrophils ESR and C-protein normal Serologic confirmation: IgM and IgG IgM: appears 1-2 days after onset of rash, remains detectable for ~1month IgG: 4-fold rise In specimens take 2-4 weeks later Viral isolation and PCR In measles not complicated by bacterial infection, the erythrocyte sedimentation rate and C-reactive protein levels are normal.

Differential Diagnoses
Rubella Adenoviruses Epstein-Barr virus Kawasaki Disease – presents with thrombocytosis, lacks Koplik spots and severe cough Drug eruptions Typical measles is unlikely to be confused with other illnesses, especially if Koplik spots are observed.

Treatment Supportive Goals of therapy: ORS, IV fluids
Hydration, oxygenation, comfort ORS, IV fluids Airway humidification and supplemental O2 Ventilatory support for croup or pneumonia Antipyretics Prophylactic antimicrobial tx is NOT indicated Antiviral therapy is NOT effective in otherwise normal patients

Treatment Measles in immunocompromised is highly lethal
Ribavarin with or without intravenous gamma globulin Measles infection in immunocompromised patients is highly lethal. Ribavirin is active in vitro against measles virus. Anecdotal reports of ribavirin therapy with or without intravenous gamma globulin suggest some benefit in individual patients. However, no controlled trials have been performed, and ribavirin is not licensed in the United States for treatment of measles.

Treatment Vitamin A Measles lowers serum retinol
Higher morbidity and mortality

Complications Morbidity and mortality are greatest in <5 years and >20 years Crowding – larger inoculum dose Severe malnutrition – suboptimal immune response Measles in immunocompromised

Complications Dehydration
Fever, diarrhea, vomiting Known to suppress PPD skin test responsiveness May have an increased rate of PTB activation

Complications Pneumonia – most common cause of death
Giant cell pneumonia caused by virus Superimposed bacterial infection Final pathway: bronchiolitis obliterans Croup, tracheitis Otitis Media – most common complication Sinusitis, mastoiditis, retropharygeal abscess Encephalitis Postinfectious immunologically mediated process Seizures (56%), lethargy (45%), coma (28%), irritability (26%) CSF: lymphocytic pleocytosis, elevated protein Approx 15% death, 20-40% mental retardation, deafness, motor disabilities Hemorrhagic or “black measles”: hemorrhagic skin eruption, fatal Myocarditis: rare Subacute Sclerosing Paraencephalitis (SSPE) The most common bacterial pathogens are S. pneumoniae, H. influenzae, and S. aureus. Following severe measles pneumonia, the final common pathway to a fatal outcome is often the development of bronchiolitis obliterans. Bronchiolitis obliterans: rare and life-threatening form of non-reversible obstructive lung disease in which the bronchioles (small airway branches) are compressed and narrowed by fibrosis (scar tissue) and/or inflammation. Signs/symptoms: dry cough, SOB, wheezing; FEV1 decreased to 16-21% of predicted values

Subacute Sclerosing Paraencephalitis (SSPE)
Rare disease Results from a persistent infection with an altered measles virus harbored in CNS for years After 7-10 years, virus regains virulence and attacks cells in CNS that offered the virus protection Inflammation and cell death  neurodegenerative process

Age of onset: <1 to <30 years Usually in children in adolescents Measles at an early age favors SSPE development Males affected twice as often as females Defective measles virus Defective or immature immune system Immature virus able to reside within neural cells for long periods

Symptoms begin 7-13 years after primary measles infection 1st stage: Subtle changes in behavior Irritability, reduced attention span, temper outbursts Fever, headache, signs of encephalitis are absent 2nd stage: massive myoclonus Extension of inflammatory process to deeper brain structures including basal ganglia 3rd stage: choreoathetosis, immobility, dystonia, lead pipe rigidity Sensorium deteriorates: dementia  stupor  coma involuntary movements disappear 4th stage Loss of centers supporting breathing, heart rate, BP Death Stage 2 Involuntary movements and repetitive myoclonic jerks begin in single muscle groups but give way to massive spasms and jerks involving both axial and appendicular muscles. Consciousness is maintained. The diagnosis of SSPE can be established through documentation of a compatible clinical course and at least 1 of the following supporting findings: (1) measles antibody detected in CSF, (2) characteristic electroencephalographic findings, or (3) typical histologic findings and/or isolation of virus or viral antigen in brain tissue obtained by biopsy or postmortem examination. Management of SSPE is primarily supportive and similar to care provided to patients with other neurodegenerative diseases. A recent large randomized clinical trial compared the use of oral inosiplex (isoprinosine) alone to oral inosiplex and intraventricular interferon-α2b. The treatment course for both groups was 6 mo. While there were no differences in the rates of stabilization or improvement at 6 mo (34% vs 35%), the study concluded that these rates were substantially better than historically reported spontaneous improvement rates of 5–10%.

Mumps Etiology Mumps virus Single-stranded pleomorphic RNA virus
Family Paramyxoviridae, Genus Rubulavirus Encapsulated in a lipoprotein envelope 7 structural proteins Hemagglutin-neuraminidase (HN) Fusion (F) Humans are the only natural host Two surface glycoproteins, HN (hemagglutinin-neuraminidase) and F (fusion), mediate absorption of the virus to host cells and penetration into cells, respectively

Mumps Transmission Spread from person-person via respiratory droplets
Virus appears in saliva 7 days before and 7 days after the onset of parotid swelling Period of maximum infectiousness: 1-2 days before to 5 days after parotid swelling

Mumps Pathology Targets the salivary glands, CNS, pancreas, testes
Thyroid, ovaries, heart, kidneys, liver, joint synovia Initial viral replication in the upper respiratory tract Spread to adjacent lymph nodes  target tissues Necrosis of infected cells Salivary gland ducts are lined with necrotic epithelium, interstitium lined with lymphocytes Swelling of tissue within the testes may result in focal ischemic infarcts. The cerebrospinal fluid (CSF) frequently contains mononuclear pleocytosis, even in individuals without clinical signs of meningitis.

Mumps Incubation Period: 12-25 days, usu. 16-18 Incubation Period
Prodromal Illness Exanthematous Phase Recovery Incubation Period: days, usu

Mumps Prodrome: 1-2 days Fever, headache, vomiting, achiness
Incubation Period Prodromal Illness Parotitis Recovery Prodrome: 1-2 days Fever, headache, vomiting, achiness

Mumps Parotid swelling appears
Incubation Period Prodromal Illness Parotitis Recovery Parotid swelling appears May be unilateral initially, but becomes bilateral 70% Peaks in 3 days, subsides over 7 days Submandibular glands may also be involved

Mumps Parotid gland is tender May be preceeded by ear pain
Angle of jaw is obscured Earlobe lifted upward and outward Sour or acidic food may enhance pain Morbiliform rash is rarely seen

Mumps Fever resolves in 3-5 days along with other systemic symptoms
Incubation Period Prodromal Illness Parotitis Recovery Fever resolves in 3-5 days along with other systemic symptoms

Diagnostics History of exposure to mumps infection Clinical findings
Elevated amylase level Relative lymphocytosis Serologic testing Increase in mumps IgG, IgM IgG may cross react with antibodies to parainfluenza virus Isolation of the virus in cell culture, PCR, immunofluorescence

Treatment No specific antiviral therapy is available for mumps
Pain control Adequate hydration Antipyretics for fever

Complications Encephalitis, meningitis, meningoencephalitis
Usually manifests 5 days after parotid swelling Infants, young children: fever, malaise, lethargy Older children: headache, meningeal signs Pancreatitis Epigastric pain, vomiting Orchitis 2nd to parotitis as a common finding After puberty, occurs 30-40% High fever, chills, pain and swelling of testes Oophoritis Uncommon in postpubertal females Severe pain

Prognosis Excellent Some fatal cases of encephalitis were reported

Prevention 2 dose MMR vaccine MMR1: mos MMR2: 4-6 years

ROSEOLA

Roseola Infantum Exanthem subitum or Sixth disease
Mild febrile exanthematous illness Occurs almost exclusively during infancy >95% occur in children younger than 3, peak at 6-15 mos Etiology Human herpesvirus (HHV) types 6 and 7 Genus: Roseolovirus Subfamily: Betaherpesvirinae Transmission Droplet From saliva of healthy persons, enters host through oral, nasal or conjunctival mucosa

Roseola Infantum Prodrome Usually asymptomatic
Mild URTI signs: minimal rhinorrhea, slight pharyngeal inflammation, mild conjunctival redness Mild cervical or occipital lymphadenoathy Mild palpebral edema

Roseola Infantum High fever (average: 39C), lasts for 3-5 days
Rhinorrhea, sore throat, abdominal pain, vomiting, diarrhea Nagayama spots: ulcers at uvulopalatoglossal junction Rash appears within hours of fever lysis Rose-colored, discrete, 2-5mm, slightly raised lesions on trunk  neck  face  proximal ext Usu. Non-pruritic, no vesicles or pustules Fades after 1-3 days

Clinical Manifestation
Abrupt onset of high fever with fussiness Rash: faint pink or rose-colored, nonpruritic, 2- to 3-mm morbilliform rash

Diagnostics Clinical presentation Serology Virus culture PCR

Treatment Supportive therapy
HHV-6 inhibit by ganciclovir, cidofovir, foscarnet (but not acyclovir) HHV-7 inhibited by cidovir and foscarnet No approved treatment Treatment is warranted for immunocompromised children with severe disease Gangciclovir, cidofovir for 2-3 weeks

RUBELLA

Rubella German measles Three-day measles

Rash similar to that of mild rubeola or scarlet fever
Enlargement and tenderness of the postoccipital, retroauricular, and posterior cervical lymph nodes

Rubella in early pregnancy may cause the congenital rubella syndrome
A serious multisystem disease with a wide spectrum of clinical expression and sequelae

Etiology RNA virus Genus Rubivirus Family Togaviridae

Epidemiology Humans are the only natural host of rubella virus
Distributed worldwide, affects both sexes equally Spread by: Oral droplet Transplacentally to the fetus

Epidemiology Peak incidence: 5-14 years of age
In closed populations, such as institutions and military barracks, almost 100% of susceptible individuals may become infected. In family settings, 50-60% of susceptible family members acquire the disease.

Epidemiology Virus is shed in nasopharyngeal secretions, blood, feces, and urine Virus is present in the nasopharynx 7 days before exanthem, and 7-8 days after its disappearance Subclinical disease is also infectious

Pathogenesis Not well understood
Virus can be found from both infected and uninfected areas of the skin Immune processes may be important

Pathogenesis Primary maternal infection during the 1st trimester: greatest risk of congenital defects <11th wk AOG: 90% End of trimester: 10-20% >16th wk AOG: low risk for congenital defects Overall risk for first trimester infection: 70% Congenital defects occur in about 90% of infants whose mothers acquire maternal infection before the 11th week of pregnancy, diminishing to about 10-20% by the end of the first trimester, with an overall risk for the trimester being about 70%. Maternal infection after the 16th week of pregnancy poses a low risk for congenital defects, although infection of the fetus may occur

Clinical Manifestations
Incubation period: days Prodromal phase of mild catarrhal symptoms is shorter than that of measles The incubation period is days. The prodromal phase of mild catarrhal symptoms is shorter than that of measles and may be so mild that it goes unnoticed. Approximately two thirds of infections are subclinical.

Retroauricular, posterior cervical, and postoccipital lymphadenopathy Most characteristic Evident at least 24 hours before the onset of rashes May last up to 1 week The most characteristic sign is retroauricular, posterior cervical, and postoccipital lymphadenopathy. No other disease causes the tender enlargement of these nodes to the extent that rubella does Lymphadenopathy is evident at least 24 hr before the rash appears and may remain for 1 wk or more.

Exanthem begins on the face and spreads quickly Discrete maculopapules present in large numbers + Large areas of flushing Pinpoint appearance over the trunk, resembling scarlet fever + mild itching Eruption + Minimal desquamation Its evolution is so rapid that the rash may be fading on the face by the time it appears on the trunk. Discrete maculopapules are present in large numbers; there are also large areas of flushing that spread rapidly over the entire body, usually within 24 hr. The rash may be confluent, particularly on the face. During the second day the rash may assume a pinpoint appearance, especially over the trunk, resembling that of scarlet fever. Mild itching may occur. The eruption usually clears by the third day. Desquamation is minimal. Rubella without a rash has been described. 24 HOURS 2ND DAY 3RD DAY

Forchheimer spots Discrete rose-colored spots on the soft palate that may coalesce into a red blush and extend over the fauses An enanthem appears in 20% of patients just before the onset of the skin rash. It consists of discrete rose-colored spots on the soft palate (Forchheimer spots) that may coalesce into a red blush and extend over the fauces.

Pharyngeal mucosa and conjunctivae are slightly inflamed No photophobia (in contrast to rubeola) Fever is low grade or absent and usually lasts only for 3 days Polyarthritis may occur with arthralgia, swelling, tenderness, and effusion but usually without any residuum NOT common: headache, malaise, anorexia Especially in older girls and women, polyarthritis may occur with arthralgia, swelling, tenderness, and effusion but usually without any residuum. Any joint may be involved, but the small joints of the hands are affected most frequently. The duration is usually several days to 2 wk; rarely it persists for months. Paresthesia also has been reported.

Differential Diagnosis
Roseola infantum (exanthem subitum) Higher fever Appearance of rash at the end of febrile episode Infectious mononucleosis Associated with generalized lymphadenopathy Characteristic atyopical lymphocytosis Enteroviral infections Accompanied by gastrointestinal or respiratory manifestations in the absence of lymphadenopathy Drug rashes History of drug intake No lymphadenopathy Because similar symptoms and rashes can occur with many other viral infections, rubella is a difficult disease to diagnose clinically except when the patient is seen during an epidemic. A history of having had rubella or rubella vaccine is unreliable; immunity should be determined by antibody testing. Particularly in its more severe forms, rubella may be confused with the mild types of scarlet fever and rubeola.

Diagnosis Clinical Objective findings:
Enlarged spleen Normal or slightly reduced WBC count Thrombocytopenia (rare) Confirmed by serology or virus culture

Diagnosis Rubella virus can be cultured from the nasopharynx and blood. It is detected by the ability of rubella-infected African green monkey kidney (AGMK) cells to resist challenge with enterovirus.

Diagnosis Hemagglutination-inhibition (HI) antibody
Latex agglutination enzyme immunoassay passive hemagglutination, and fluorescent immunoassay Hemagglutination-inhibition (HI) antibody has been the reference method of determining immunity to rubella, but newer methods that are easier to perform are now used more commonly. Latex agglutination, enzyme immunoassay, passive hemagglutination, and fluorescent immunoassay appear to be equal or superior to the HI test in sensitivity.

Diagnosis Immunoglobulin (Ig) M antibodies
detectable in the first few days of illness Also useful for the diagnosis of congenital rubella syndrome. Seroconversion, or a fourfold increase in IgG titer, is diagnostic. Immunoglobulin (Ig) M antibodies are detectable in the first few days of illness and are considered diagnostic. Detection of IgM antibodies, which do not cross the placenta, in the newborn is especially useful for the diagnosis of congenital rubella syndrome. Seroconversion, or a fourfold increase in IgG titer, is diagnostic.

Treatment Supportive treatment No specific antiviral therapy
Antipyretics for fever

Prognosis Excellent. Infection usually confers permanent immunity, although reinfection may occur.

Complications Encephalitis
Occurs in about 1 in 6,000 cases Overall mortality rate of 20% Symptoms usually resolve within 1-3 wk without neurologic sequelae Thrombocytopenic purpura occurs at an overall rate of 1 in 3,000 cases. Encephalitis similar to that seen with measles occurs in about 1 in 6,000 cases. The severity is highly variable, and there is an overall mortality rate of 20%. Symptoms in survivors usually resolve within 1-3 wk without neurologic sequelae.

Complications The most important consequence of rubella in a pregnant woman is congenital rubella syndrome. Progressive rubella panencephalitis is a persistent, slowly progressive rubella infection of the central nervous system

Congenital Rubella Syndrome
Intrauterine growth retardation: most common manifestations Common findings: Cataracts Myocarditis and structural cardiac defects Blueberry muffin skin lesions Sensorineural hearing loss Meningoencephalitis Congenital rubella affects virtually all organ systems. The most common manifestation is intrauterine growth retardation. Other common findings include cataracts, bilateral or unilateral, which are frequently associated with microphthalmia; myocarditis and structural cardiac defects (e.g., patent ductus arteriosus or pulmonary artery stenosis); "blueberry muffin" skin lesions, similar to those seen in congenital cytomegalovirus infection; hearing loss from sensorineural deafness; and meningoencephalitis. Persistent infection leads to pneumonia, hepatitis, bone lucencies, thrombocytopenic purpura, and anemia. Later sequelae include motor and mental retardation.

Diagnosis: Rubella-specific IgM antibody in the neonatal serum, or by culturing rubella virus from the infant (nasopharynx, urine, or tissues) Isolating the virus from amniotic fluid or by identification of rubella-specific IgM in cord blood. The diagnosis is confirmed by finding rubella-specific IgM antibody in the neonatal serum, or by culturing rubella virus from the infant (nasopharynx, urine, or tissues). Virus can be shed in the urine for 1 yr or longer. Prenatal diagnosis of fetal rubella infection can be made either by isolating the virus from amniotic fluid or by identification of rubella-specific IgM in cord blood.

Prognosis Better for infants with fewer stigmata of the syndrome, presumably those who were initially infected later in gestation. Only 30% of infants with encephalitis appear to escape residual neuromotor deficitis, including an autistic syndrome

Reinfection The incidence of reinfection
3-10% on exposure to wild virus among those with a history of previous rubella 14-18% among those immunized with the RA 27/3 vaccine. May lead only to an IgG booster response, to both an IgM and IgG response, or to clinical rubella. The incidence of reinfection on exposure to wild virus is 3-10% among those with a history of previous rubella and 14-18% among those immunized with the RA 27/3 vaccine. Reinfection may lead only to an IgG booster response, to both an IgM and IgG response, or to clinical rubella.

Prevention Rubella vaccine is derived from the RA 27/3 strain of rubella virus Induces antibody in more than 99% of seronegative recipients and has protective efficacy in more than 90% Vaccine virus may be shed from the nasopharynx in low titers for as long as days after vaccination The vaccine induces antibody in more than 99% of seronegative recipients and has protective efficacy in more than 90%. Vaccine virus may be shed from the nasopharynx in low titers for as long as days after vaccination, although there is no evidence of communicability.

Prevention MMR 1st: recommended at mo of age. 2nd: recommended routinely at 4-6 yr of age but may be administered at any time during childhood provided at least 4 wk have elapsed since the first dose. Pregnant women should not be given live rubella virus vaccine and should avoid becoming pregnant for 3 mo after they have been vaccinated

Prevention Symptoms that may follow rubella immunization include
Fever (5-15%), Rash (5%), Lymphadenopathy, and Arthralgias and arthritis Symptoms that may follow rubella immunization include fever (5-15%), rash (5%), lymphadenopathy, and arthralgias and arthritis. Joint involvement, usually seen in the small peripheral joints days after vaccination, is uncommon in children but occurs frequently in postpubertal females with both arthralgias (25%) and transient arthritis (10%) being reported. It may last for weeks

Postexposure prophylaxis
Nonpregnant susceptible contacts of persons with rubella should be vaccinated does not prevent infection but ensures protection for future rubella exposures All pregnant women, regardless of immunization history, should make every effort to avoid exposure to rubella. Nonpregnant susceptible contacts of persons with rubella should be vaccinated. This does not prevent infection but ensures protection for future rubella exposures. All pregnant women, regardless of immunization history, should make every effort to avoid exposure to rubella.

ERYTHEMA INFECTIOSUM

Parvovirus B19 Erythema infectiosum Fifth disease

Etiology Parvovirus B19 Only Parvovirus pathogenic in humans
Genus Erythrovirus Family Parvoviridae Only Parvovirus pathogenic in humans Composed of an icosahedral protein capsid without an envelope that contains single-stranded DNA It is relatively heat- and solvent-resistant. Replicate in mitotically-active cells require host cell factors present in late S phase to replicate B19 is composed of an icosahedral protein capsid without an envelope that contains single-stranded DNA approximately 5.5 kb in length. It is relatively heat- and solvent-resistant. It is antigenically distinct from other mammalian parvoviruses, and there is only one known serotype. Parvoviruses replicate in mitotically-active cells. Because of their limited genome, they require host cell factors present in late S phase to replicate.

Epidemiology Most prevalent in school-aged children Transmission:
70% of cases occurring between 5 and 15 yr of age Transmission: respiratory route (large droplet) Other mode: Blood and blood products Fomite Transmission of B19 is by the respiratory route, presumably via large droplet spread from nasopharyngeal viral shedding. B19 is transmissible in blood and blood products, which has been documented among children with hemophilia receiving pooled donor clotting factor. Given the resistance of the virus to solvents, fomite transmission could be important in childcare and other group settings, but this mode of transmission has not been documented.

Pathogenesis Erythroid cell line
Primary target Specifically erythroid precursors near the pronormoblast stage Viral infection produces lysis of these cells progressive depletion and a transient arrest of erythropoiesis Erythrocyte P blood group antigen serves as a cellular receptor for the virus. Found in Endothelial cells, placenta, and fetal myocardial cells also possess this antigen The primary target of B19 infection is the erythroid cell line, specifically erythroid precursors near the pronormoblast stage. Viral infection produces lysis of these cells, leading to a progressive depletion and a transient arrest of erythropoiesis. The virus has no apparent effect on the myeloid cell line. The tropism for erythroid cells is related to the erythrocyte P blood group antigen, which serves as a cellular receptor for the virus. Endothelial cells, placenta, and fetal myocardial cells also possess this antigen. Thrombocytopenia and neutropenia are often observed clinically, but their pathogenesis is unexplained.

7-11 days 17-18 days Pathogenesis
Biphasic illness 7-11 days Viremia, nasopharyngeal viral shedding, drop in reticulocyte count Fever, malaise, rhinorrhea 17-18 days Rash associated with arthralgia Humoral immunity is crucial in controlling infection. Specific immunoglobulin M (IgM) appears within 1-2 days followed by anti-B19 IgG, leading to control of the infection, restoration of reticulocytosis, and a rise in serum hemoglobin.

Pathogenesis B19 is associated with nonimmune fetal hydrops and stillbirth in women experiencing a primary infection Not teratogenic B19 is associated with nonimmune fetal hydrops and stillbirth in women experiencing a primary infection but does not appear to be teratogenic. Like most mammalian parvoviruses, B19 can cross the placenta and cause fetal infection during primary maternal infection. Parvovirus cytopathic effects are seen primarily in erythroblasts of the bone marrow and sites of extramedullary hematopoiesis in the liver and spleen. Fetal infection can presumably occur as early as 6 wk of gestation, when erythroblasts are first found in the fetal liver; after the 4th gestational month hematopoiesis switches to the bone marrow.

Most common manifestation: erythema infectiosum Benign self-limited exanthematous Incubation period: 4-28 days (ave: days) The preceding four exanthems were measles, scarlet fever, rubella and Filatov-Dukes disease (an atypical scarlet fever), with roseola infantum as the "sixth disease."

Low-grade fever Headache Symptoms of mild URTI Hallmark: characteristic rash

Spares palms and soles Prominent on extensor surfaces Afebrile and NOT ill-appearing Erythematous facial flushing – “slapped cheek” Spreads to trunk and proximal extremities as diffuse macular erythema Central clearing of macular lesions – “lacy, reticulated” The rash resolves spontaneously without desquamation but tends to wax and wane over 1-3 wk. It can recur with exposure to sunlight, heat, exercise, and stress. Lymphadenopathy and atypical papular, purpuric, vesicular rashes are also described.

Papular-purpuric "gloves and socks" syndrome (PPGSS) Fever Pruritus Painful edema and erythema localized to the distal extremities in a distinct glove and sock distribution Acral petechiae and oral lesions PPGSS is characterized by fever, pruritus, and painful edema and erythema localized to the distal extremities in a distinct glove and sock distribution, followed by acral petechiae and oral lesions. The syndrome is self-limited and resolves within a few weeks. Initially described in young adults, a number of reports in children have since been published. In those linked to B19 infection, the eruption is accompanied by serologic evidence of acute infection.

Diagnosis Clinical Serologic tests
B19-specific IgM: persists for 6-8 wk Anti-B19 IgG: marker of past infection/immunity Anti-B19 IgM: best marker of recent/acute infection seroconversion of anti-B19 IgG antibodies can also be used to confirm recent infection B19-specific IgM develops rapidly after infection and persists for 6-8 wk. Anti-B19 IgG serves as a marker of past infection or immunity. Determination of anti-B19 IgM is the best marker of recent/acute infection on a single serum sample; seroconversion of anti-B19 IgG antibodies in paired sera can also be used to confirm recent infection. Serologic diagnosis is unreliable in immunocompromised patients; diagnosis in these patients requires methods to detect viral DNA.

Diagnosis Cannot be isolated by culture
PCR or nucleic acid hybridization are necessary Prenatal diagnosis of B19-induced fetal hydrops can be accomplished by detection of viral DNA in fetal blood by these methods or visualization of viral particles by immune electron microscopy.

Rubella Measles Enteroviral infections Juvenile rheumatoid arthritis SLE The rash of erythema infectiosum must be differentiated from that of rubella, measles, enteroviral infections, and drug reactions. Rash and arthritis in older children should prompt consideration of juvenile rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue disorders.

Treatment No specific antiviral therapy
Administration of IVIG may give only a temporary remission, and periodic re-infusions may be required.

Complications Arthralgia or arthritis Thrombocytic purpura
May persist after the rash Thrombocytic purpura Aseptic meningitis Virus-associated hemophagocytic syndrome

Prevention Children with erythema infectiosum are not likely to be infectious at presentation because the rash and arthropathy represent immune-mediated, postinfectious phenomena. No vaccine No data to support post-exposure prophylaxis Children with erythema infectiosum are not likely to be infectious at presentation because the rash and arthropathy represent immune-mediated, postinfectious phenomena. Isolation and exclusion from school or childcare are unnecessary and ineffective after diagnosis

VARICELLA

Varicella-Zoster Primary Reactivation Varicella (chickenpox)
Establishment of lifelong latent infection of sensory ganglion neurons Reactivation herpes zoster (shingles) Varicella-zoster virus (VZV) causes primary, latent, and recurrent infections. The primary infection is manifested as varicella (chickenpox) and results in establishment of a lifelong latent infection of sensory ganglion neurons. Reactivation of the latent infection causes herpes zoster (shingles).

Etiology Neurotropic human herpesvirus Double-stranded DNA genomes
VZV is a neurotropic human herpesvirus with similarities to herpes simplex virus, which is also an α-herpesvirus. These viruses are enveloped with double-stranded DNA genomes that encode more than 70 proteins, including proteins that are targets of cellular and humoral immunity.

Epidemiology Within households, transmission to susceptible individuals occurs at a rate of 65-86%; More casual contact is associated with lower attack rates among susceptible children Within households, transmission of VZV to susceptible individuals occurs at a rate of 65-86%; more casual contact, such as occurs in a school classroom, is associated with lower attack rates among susceptible children

Epidemiology Contagious period:
From hr BEFORE the rash appears Until 3-7 days after onset of rash (crusted vesicles) Susceptible children may also acquire varicella after close, direct contact with adults or children who have herpes zoster. Patients with varicella are contagious from hr before the rash appears and until vesicles are crusted, usually 3-7 days after onset of rash. Susceptible children may also acquire varicella after close, direct contact with adults or children who have herpes zoster.

Epidemiology Lifetime risk for herpes zoster is 10-15%
75% of cases occurring after 45 yr of age The lifetime risk for herpes zoster for individuals with a history of varicella is 10-15%, with 75% of cases occurring after 45 yr of age.

Pathogenesis Transmission: Respiratory secretions (airborne)
Fluid of skin lesions (direct contact) VZV is transmitted in respiratory secretions and in the fluid of skin lesions either by airborne spread or through direct contact. Primary infection (varicella) results from the respiratory inoculation of virus.

Pathogenesis Incubation period: 10-21 days
Virus replicates in the respiratory tract followed by a brief subclinical viremia During the late incubation period, virus is transported back to respiratory mucosal sites facilitating transmission even before appearance of rash Second viremic phase: Widespread cutaneous lesions During the early part of the day incubation period, virus replicates in the respiratory tract followed by a brief subclinical viremia. VZV is also transported back to respiratory mucosal sites during the late incubation period, permitting spread to susceptible contacts before the appearance of rash.

Pathogenesis VZV establishes latent infection in sensory ganglia cells in all individuals who experience primary infection. Subsequent reactivation: herpes zoster a vesicular rash that usually is dermatomal necrotic changes may be produced in the associated ganglia VZV establishes latent infection in sensory ganglia cells in all individuals who experience primary infection. Subsequent reactivation of latent virus causes herpes zoster, a vesicular rash that usually is dermatomal in distribution. During herpes zoster, necrotic changes may be produced in the associated ganglia.

Acute febrile rash illness Variable severity but usually self-limited Herpes zoster, uncommon in children, causes localized cutaneous symptoms Varicella is an acute febrile rash illness, common in children who have not been immunized. It has variable severity but is usually self-limited Herpes zoster, uncommon in children, causes localized cutaneous symptoms, but may disseminate in immunocompromised patients.

Illness usually begins days after exposure The illness usually begins days after exposure, although the incubation period can range from days.

Fever, malaise, anorexia, headache, and occasionally mild abdominal pain may occur hr before the rash appears. Fever and other systemic symptoms persist during the first 2-4 days after the onset of the rash.

Lesions appear first on the scalp, face, trunk Characteristic: lesions in various stages Initial: pruritic erythematous macules Papular stage: clear, fluid-filled vesicles Clouding and umbilication Varicella lesions often appear first on the scalp, face, or trunk. The initial exanthem consists of intensely pruritic erythematous macules that evolve through the papular stage to form clear, fluid-filled vesicles. Clouding and umbilication of the lesions begin in hr. While the initial lesions are crusting, new crops form on the trunk and then the extremities; the simultaneous presence of lesions in various stages of evolution is characteristic of varicella

Distribution: central or centripetal As opposed to smallpox where rashes are prominent on the face and distal extremities

Hypopigmentation or hyperpigmentation of lesion sites persists for days to weeks in some children, but severe scarring is unusual unless the lesions were secondarily infected

Includes vesicular rashes caused by other infectious agents herpes simplex virus enterovirus, or Staphylococcus aureus; Drug reactions Contact dermatitis Insect bites.

Diagnosis Leukopenia is typical during the first 72 hours; it is followed by a relative and absolute lymphocytosis. Results of liver function tests are also usually (75%) mildly elevated

Diagnosis VZV can be identified quickly by direct fluorescence assay (DFA) of cells from cutaneous lesions, which is widely available, and by polymerase chain reaction (PCR) amplification testing. Although multinucleated giant cells can be detected with nonspecific stains (Tzanck smear), they have poor sensitivity and do not differentiate VZV and herpes simplex virus infections. VZV can be identified quickly by direct fluorescence assay (DFA) of cells from cutaneous lesions, which is widely available, and by polymerase chain reaction (PCR) amplification testing. Although multinucleated giant cells can be detected with nonspecific stains (Tzanck smear), they have poor sensitivity and do not differentiate VZV and herpes simplex virus infections.

Diagnosis Infectious virus may be recovered using tissue culture methods; newer methods have decreased time needed for culture from 7-10 days to 3-4 days. VZV immunoglobulin G (IgG) antibodies can be detected by several methods and a 4-fold rise in IgG antibodies is also confirmatory of acute infection. VZV IgG antibody tests can also be valuable to determine the immune status of individuals whose clinical history of varicella is unknown or equivocal. Infectious virus may be recovered using tissue culture methods; newer methods have decreased time needed for culture from 7-10 days to 3-4 days. VZV immunoglobulin G (IgG) antibodies can be detected by several methods and a 4-fold rise in IgG antibodies is also confirmatory of acute infection. VZV IgG antibody tests can also be valuable to determine the immune status of individuals whose clinical history of varicella is unknown or equivocal.

Treatment Antiviral treatment modifies the course of both varicella and herpes zoster. Acyclovir Foscarnet for acyclovir-resistant VZV

Treatment Oral therapy with acyclovir (20 mg/kg/dose; maximum: 800 mg/dose) given as 4 doses per day for 5 days should be used to treat uncomplicated varicella To be most effective, treatment should be initiated as early as possible, preferably within 24 hr of the onset of the exanthem. However, acyclovir therapy is not recommended routinely by the American Academy of Pediatrics for treatment of uncomplicated varicella in the otherwise healthy child because of the marginal benefit, the cost of the drug, and the low risk of complications.

Complications Bacterial super-infection Pneumonia Encephalitis
Bleeding disorders Congenital infection Life-threatening perinatal infection

21 Nov 2013 Danize Buemio Mary April Chan

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21 Nov 2013 Danize Buemio Mary April Chan

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