What are some DNA viruses that cause rash?
-Parvovirus B19 (Fifth Disease)-non, enveloped, ssDNA
-Human HerpesVirus 6/7 (Roseola)- enveloped, large dsDNA
What are some RNA viruses that cause rash?
-Paramyxovirus (Measles) -enveloped, negative sense ssRNA
-Togavirus (Rubella)- enveloped, +ssRNA
-Picornavirus (enteroviruses)- non enveloped, +ssRNA
What diseases can Picornaviruses cause?
-Coxsackie A (hand, Foot, and Mouth Disease)
-Enterovirus/ECHO viruses (transient, non-descript rashes) (also account for 90% of viral meningitis cases)
What is Erthema Infectiosum (Fifth Disease)?
Disease caused by Parvovirus B19 that is dependent on the S-phase of host for replication and replicated in RBC precursors (but not mature RBCs)
How is Fifth Disease contracted?
Contracted via respiratory tract secretions, percutaneous exposure to blood or blood products, and vertical transmission from mother to fetus
What are the phases of a B19 infection?
There is a roughly 1-2 week incubation period after contracting the bug followed by:
1) Lytic, infectious phase (lasting roughly a week)-most contagious and BEFORE the rash
a short intermediate period where it is very difficult to isolate the virus from any site
2) Non-infectious, immunologic phase (CD4 mediated)
How does Fifth disease present?
aka slapped cheek syndrome (The name "fifth disease" comes from its place on the standard list of rash-causing childhood diseases)
-Starts with a low-grade fever, headache, rash, and cold-like symptoms, such as a runny or stuffy nose. These symptoms pass, then a few days later the rash appears. The bright red rash most commonly appears in the face, particularly the cheeks. Occasionally the rash will extend over the bridge of the nose or around the mouth. In addition to red cheeks, children often develop a red, lacy rash on the rest of the body, with the upper arms, torso, and legs being the most common locations. The rash typically lasts a couple of days and may itch; some cases have been known to last for several weeks. *Patients are usually no longer infectious once the rash has appeared*
Teenagers and adults may present with a self-limited arthritis. It manifests in painful swelling of the joints that feels similar to arthritis. Older children and adults with fifth disease may have difficulty in walking and in bending joints such as wrists, knees, ankles, fingers, and shoulders.
What are the potential complications of Fifth's Disease?
In pregnant women, infection in the first trimester has been linked to hydrops fetalis, causing spontaneous miscarriage.
In people with sickle-cell disease or other forms of chronic hemolytic anemia such as hereditary spherocytosis, infection can precipitate an aplastic crisis.
Those who are immuno-compromised (HIV/AIDS, chemotherapy) may be at risk for complications (anemia) if exposed.
What is Hydrops fetalis?
A serious fetal condition defined as abnormal accumulation of fluid in 2 or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema
What is measles virus?
A member of the Morbillivirus genus of the Paramyxoviridae family that primarily uses CD46, SLAM, and nectin-4 receptors (note that infection of nectin-4 on skin cells causes the rash) ON IMMUNE CELLS to infect and forms intracellular inclusion bodies. Very contagious
This disease REQUIRES a large population size
How does Measles present?
This is mostly a pediatric disease that presents with initial signs and symptoms typically including 4+ days of fever, often greater than 40 °C (104.0 °F), cough, runny nose, and inflamed eyes. Two or three days after the start of symptoms, small white spots may form inside the mouth, known as Koplik's spots. A red, flat rash which usually starts on the face and then spreads to the rest of the body typically begins three to five days after the start of symptoms.
Symptoms usually develop 10–14 days after exposure to an infected person and last 7–10 days
What are these?
Koplik's spots in the mouth of a measles patient. These are pathognomonic but only temporary!
How is measles contracted?
Measles is an airborne disease which spreads easily through the coughs and sneezes of those infected. It may also be spread through contact with saliva or nasal secretions.
Nine out of ten people who are not immune and share living space with an infected person will catch it. People are infectious to others from four days before to four days after the start of the rash (Rash coincides with a strong cell-mediated immune response and virus clearance). People usually do not get the disease more than once.
How can be measles be prevented?
MMR vaccine, if administered within 72 hours of initial measles exposure, or immunoglobulin (IG), if administered within six days of exposure, may provide some protection or modify the clinical course of disease.
Tips for remembering the clinical presentation of measles. What causes the rash?
The classic signs and symptoms of measles include four-day fevers (the 4 D's) and the three C's—cough, coryza (head cold, fever, sneezing), and conjunctivitis (red eyes)
The rash is caused by a cytotoxic T cell (CD8) response against infected endothelial cells in the skin
What are the potential complications of measles?
Complications with measles are relatively common, ranging from mild complications such as diarrhea to serious complications such as pneumonia (either direct viral pneumonia or secondary bacterial pneumonia), bronchitis (either direct viral bronchitis or secondary bacterial bronchitis), otitis media, and corneal ulceration (leading to corneal scarring).
Complications are usually more severe in adults who catch the virus.
Other measles complications?
1) Immune Suppression
-Delayed-type hypersensitivity responses are suppressed (e.g. TB skin test)
-Occurs before onset of the rash and continues for ~1 month
2) Production of antibody and cellular immune responses to new antigens are also impaired
-Infection of monocytes and other immune effector cells are probably the primary cause of measles virus-induced immune suppression
What are the potential neurological MV complications?
-Acute disseminated encephalomyelitis (ADEM) or postinfectious encephalomyelitis (PIE)
-Measles Inclusion Body Encephalitis (MIBE)
-Subacute Sclerosing Panencephalitis (SSPE)
What is Acute disseminated encephalomyelitis (ADEM) or postinfectious encephalomyelitis (PIE)?
An autoimmune demyelinating diseases occuring in roughly 1:1000 infections that results from a hyperactive immune response to myelin absic protein resulting in colvulsions, deafness, and mental retardation
What do measles includion body encaphalitis (MIBE) and subacute sclerosing panencephalitis (SSPE) result from?
persistance MV infection in the brain (mutations in the matrix, H, and F proteins help establish MV CNS infections!)
What is the dosing schedule for the MMR vaccine?
SubQ live-attenuated measles provides life-long immunity
1) 12-15 months (can be earlier but not before 6 months)
2) 4-6 yrs
Why is the measles vaccine effective for life?
MMR are antigenically stable monotypic viruses. (There are different strains of MV, but neutralizing antibody to one protects an individual against all circulating strains)
How does Rubella present?
This disease is often mild with half of people not realizing that they are sick. A rash may start around two weeks after exposure and last for three days. It usually starts on the face and spreads to the rest of the body. The rash is not as bright as that of measles and is sometimes itchy. Swollen lymph nodes are common and may last a few weeks. A fever, sore throat, and fatigue may also occur. In adults joint pain is common.
How is Rubella transmitted?
Primarily via aerosols and the initial replicaiton occurs in the upper respiratory tract mucosa and the nasopharyngeal lymph nodes
Describe the timeline of rubella progression
–Incubation period is 7-9 days
–Viremia develops and virus can be isolated from the stool and the nasopharynx
–Rash develops at 16-21 days
–Virus shedding continues after the rash disappears and continues for ~1 month following initial exposure
What are some potential complications of rubella?
-Congenital birth defects of fetus (highest risk in 1st and 2nd trimester) that have manifestations including mental retardation, motor disabilities, hearing loss, cataracts, and heart disease (aka congenital rubella syndrome)
Following infection of the placenta, the virus spreads to the fetus and replicates in virtually all tissues and organs
What are the four major groups of enterovirus?
Coxsakievirus (Groups A and B)
How are enteroviruses differentiated from rhinoviruses?
Enteroviruses are acid stabile and have less strignent growth requirements (can grow in human and primate cell lines and at 37C)
How are Enteroviruses contracted?
Spread by oral-fecal route (enteroviruses and coxsackie) or by aerosol contamination of fomites (coxsackie viruses)
What is the typical progression of enterovirus infection?
Initially enteroviruses replicate in lymphoid tissue of the upper respiratory tract (tonsils and lymph nodes) and the gut (Peyer's patches and small intestine)( Often isolated from throat cultures). This is followed by viremia resulting in infection of many organs including:
•Spinal cord, brain, meninges
Virus continues to be released in stool for several weeks
How do Enterovirus infections typically present?
Many cases are asymptomatic. In those with symptoms, there is about a 2-10 day incubation period followed by onset of fever, sore throat, and malaise that wanes before the onset of headache and stiff neck (disease tends to eb bi-phasic)
What is Hand, Foot, and Mouth Disease?
Disease caused by coxsackievirus A16, A6, and enterovirus 71 that presents as ulcerative lesions on the tonsila and uvula (herpangina), as well as lesions on the hands and/or feet and constitutive symptoms of fever, HA, sore throat.
The sisease is self-limiting and requires only symptomatic management, but it is HIGHLY CONTAGIOUS (keep out of school)
One thing that can tip you off to enterovirus is there consistent commonality to seasons, particularly _____ and ______
Summer and Fall
What is Mumps Virus?
aka epidemic parotitis, a viral disease caused by the mumps virus. Initial signs and symptoms often include fever, muscle pain, headache, and feeling tired. This is then usually followed by painful swelling of one or both parotid glands.
Symptoms typically occur 16 to 18 days after exposure and resolve after seven to ten days. Symptoms in adults are often more severe than in children. About a third of people have mild or no symptoms.
Notes on contraction of Mumps
Initial site of infection is the mucosal epithelium of the nasopharynx and upper respiratory tract (Mumps is not as infectious as measles)
Virus initially replicates in the upper respiratory mucosa, then spreads to the draining lymph nodes
Virus is shed in the saliva ~6 days before onset of clinical disease
What are some complications of Mumps?
Approximately half of mumps infections result in some virus replication in the CNS (Aseptic meningitis (resolves after 3-10 days) and Infection of cochlea leads to deafness (~1/20,000))
•Major complication seen in post-pubertal men is symptomatic gonadal involvement (testes swell due to viral replication causing edema and tissue damage that can leave them STERILE)
What are morbilliform eruptions?
The most common cutaneous rxn to drugs (responsible for 75% of drug rashes) that result from type IV immune reactions. Less frequently, drugs can cause urticaria/angioedema, anaphylaxis, and phototoxic reactions.
What drugs are most likely to trigger autoimmune bullous diseases (e.g. pemphigus, bullois pemphigoid, linear IgA bullous dermatosis)
What HLA groups are thought to predispose one to drug rash rxns?
B*1502, B*5801, or B*5701
Can reactivate in immunocompromised people!
A. Aka 6th Disease/Exanthema subitum. Rosela is most likely to present in children aged 6 months to 4 yrs causes by HHV 6/7
ØMode of transmission unknown (possibly from nasopharyngeal secretions)
How does Roseola present?
Typically begins with a sudden high fever (39–40 °C; 102.2-104 °F). This can cause, in rare cases, febrile convulsions (also known as febrile seizures or "fever fits") due to the sudden rise in body temperature, but in many cases the child appears normal. After a few days the fever subsides, and just as the child appears to be recovering, a red rash appears. This usually begins on the trunk, spreading to the legs and neck.
Describe the rash of roseola
The rash is not itchy and may last 1 to 2 days.
In contrast, a child suffering from measles would usually appear more infirm, with symptoms of conjunctivitis, coryza, and a cough, and their rash would affect the face and last for several days. Liver dysfunction can occur in rare cases.
ØReactivation of HHV-6 with drug exposure can lead to _______
drug-induced hypersensitivity syndrome (DIHS)
What are the complications of roseola?
ØHHV-6 establishes life-long latency and can become reactivated later in life or if an individual is immunocompromised. This reactivation has been associated with many clinical manifestations.
ØReactivation can occur in locations throughout the body, including the brain, lungs, heart, kidney and gastrointestinal tract. In some cases, HHV-6 reactivation in the brain tissue can cause cognitive dysfunction, permanent disability and death.
ØReactivation occurs in 33-48% of patients undergoing hematopoietic stem-cell transplantation.