21 fever with rash

• Varicella/Herpes zoster


  Caused by Varicella zoster virus (VZV), a DNA virus in the Herpesviridae family

  
• Primary varicella (chickenpox) demonstrates a prominent seasonal pattern in temperate climates, most common in the winter and spring
• Chickenpox also demonstrates periodic epidemics, followed by years of lower incidence
• Chickenpox most common in childhood with a peak incidence between 5 and 9 years of age
• Pathogenesis of Varicella


  1. Initial infection in conjunctivae or upper respiratory tract

  2. Virus replicates locally for 4-6 days

  3. Primary viremia transmits virus throughout body

  4. Secondary viremia releases virus into cutaneous tissues, causing characteristic vesicles

  
• Incubation period


  Interval between infection and appearance of vesicular rash, usually 14-15 days, range 10-20 days

  
• Average number of skin lesions ranges 200-300 in index case, up to 500+ in secondary cases

  
• Infants <1 year, older teenagers and adults may have more severe disease
• Most frequent complication in healthy child is bacterial infection
• Viral sequelae can involve all organ systems (pneumonitis, hepatitis, arthritis, pericarditis, glomerulonephritis, orchitis, nervous system)

  
• Acute cerebellar syndrome is most common VZV-induced neurologic disease in children
• Tzanck smear


  Reveals multinucleated giant cells, indicating cell-cell fusion mediated by VZV glycoproteins

  
• Herpes zoster


  Reactivation of VZV from dorsal root ganglia of sensory nerves
• Herpes zoster complications include secondary bacterial infection, scarring, necrotizing fasciitis, post-herpetic neuralgia, eye complications, Ramsay Hunt syndrome

  
• Exanthema subitum (Sixth disease, Roseola infantum)


  Caused by human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7)

  
• Characteristic feature of roseola is abrupt rash onset with fever resolution, rash consists of blanching rose-pink macules/papules with white halo

  
• Berliner's sign (periorbital edema) may be a useful diagnostic clue for roseola
• Laboratory studies generally not required for roseola, leucopenia may be present
• Measles (Rubeola)


  Caused by a non-segmented negative polarity RNA virus in the Paramyxoviridae family

  
• Rubella (German measles)


  Caused by a single-stranded RNA virus in the Matonaviridae family

  
• Henoch-Schönlein purpura


  A condition characterized by a rash, joint pain, and gastrointestinal and kidney problems
• Kawasaki disease


  An illness that causes inflammation in the walls of blood vessels throughout the body
• Work up for measles

  1. Positive serologic test for serum measles IgM antibody

  2. Significant rise in measles IgG antibody between acute and convalescent titers

  3. Isolation of measles virus in culture

  4. Detection of measles virus RNA by reverse transcription polymerase chain reaction (RT-PCR)

  
• Rubella (German measles)


  A contagious viral infection that causes a red rash

  
• In 2004, rubella was officially declared eliminated from the United States; in 2015, rubella was eliminated from the Americas
• Considerable progress has occurred toward rubella elimination worldwide
• By the end of 2021, 173 of 195 countries (89 percent) had introduced rubella-containing vaccines (RCV) into national childhood immunization programs, and 93 (48 percent) of countries verified eliminating transmission of rubella

  
• Despite this progress, rubella cases continue to occur, with 10,194 cases occurring globally in 2020
• Rubella virus


  A single-stranded RNA virus in the family Matonaviridae
• Rubella


  • Acquired via inhalation of infectious large particle aerosols
  • Incubation period is typically 14 to 18 days (range 12 to 23 days)
  • Up to 50% of infections are subclinical
  • Individuals with infection may shed the virus and are potentially contagious for one week before to two weeks after the rash is noted
  • After entry into the upper respiratory tract, viral replication occurs within the nasopharyngeal mucosa and regional lymph nodes, followed by viraemia and spread to skin and other organs

  
• Rubella rash


  • Erythematous maculopapular rash that initially appears on the face, rapidly generalizes within 24 hours and then fades, often within 3 days
  • Lesions do not coalesce and are fainter than the lesions of measles
  • Conjunctivitis and mucosal erythema may occur

  
• Rubella complications


  • Arthralgias/arthritis, thrombocytopenia and encephalitis (1 in 6000)
• Rubella work up


  1. Viral detection by PCR

  2. Rubella‐specific IgM antibody or a significant rise in immunoglobulin G (IgG) antibody from paired acute and convalescent sera

  
• Erythema infectiosum (Fifth disease)

  A viral illness caused by parvovirus B19 that results in a characteristic red rash

  
• Parvovirus B19


  A single-stranded DNA virus that causes erythema infectiosum

  
• Parvovirus B19 transmission


  • Transmitted from person to person via the respiratory route (respiratory secretions, saliva), fomites
  • Young children are the main source of respiratory-acquired parvovirus B19
  • Incubation period one and two weeks but can be as long as three weeks
  • Patients are most contagious during the phase of active viral replication and viral shedding, which occurs approximately 5 to 10 days after exposure and usually lasts approximately 5 days

  
• Erythema infectiosum clinical features

  • Begins with nonspecific prodromal symptoms, such as fever, coryza, headache, nausea, and diarrhea
  • Two to five days later, the classic erythematous malar rash appears with relative circumoral pallor (the so-called slapped cheek rash)
  • This facial rash is often followed several days later by a reticulated or lacelike rash on the trunk and extremities
  • The rash is thought to be immunologically mediated
  • Symptoms can last for months, or rarely even years, in some patients
  • Recrudescence of the rash after nonspecific stimuli is a typical feature
  • Neurologic complications include CNS and encephalitis
  • In adults, particularly women, acute arthritis with or without a rash may occur
  • Transient aplastic crisis, in which the temporary suspension of erythropoiesis results in severe anemia and related complications

  
• Erythema infectiosum work up

  1. In immunocompetent children who present with the classic malar rash, the presumptive diagnosis can be made on the clinical features alone

  2. Serology: parvovirus B19-specific IgM antibody (if needed)

  3. In the setting of transient aplastic crisis or chronic pure red cell aplasia, the diagnosis is made by detection of high levels of parvovirus B19 DNA through nucleic acid amplification testing (NAAT)

  
• The incidence of KD is greatest in children who live in East Asia or are of Asian ancestry living in other parts of the world
• Kawasaki disease etiology


  • The etiology remains unknown, but several factors have been postulated including an immunologic response, infectious etiology, and genetic factors