Viral Exanthems and Enanthems

• Learning Objectives:
• Describe classic presentations of common viral exanthems and enanthems.
• Discuss the clinical importance of viral exanthems and enanthems.
• List specific features of some viral rashes to help differentiate between them.

Definition of Terms

• Exanthem means skin rash.
• Enanthem is a rash or swelling on a mucous membrane.
• Macule: Flat colored spots on the skin.
• Papules: Slightly raised lesions of the skin.
• Maculo-papular: Some lesions are flat; others are raised.
• Pustules: Raised lesions with pus inside.
• Vesicles: Raised lesions with serous fluid inside.
• Nodules: Hard swellings.
• Warts: Papillomatous, verrucous swellings.

Viruses Causing Skin Diseases

• Macular/Maculo-papular Rash: Caused by Measles virus, Rubella virus, Arboviruses, Human herpesvirus 6, Human parvovirus B19, Epstein-Barr virus, Cytomegalovirus, Ebola, Lassa.
• Vesicles: Caused by Herpes simplex virus, Varicella-zoster virus, Coxsackie A viruses, poxvirus
• Pustules: Monkeypox virus, Cowpox virus, Vaccinia virus can cause pustules.
• Nodules can be caused by Molluscum contagiosum, Milker's nodules, Orf, Tanapox.
• Warts: Papillomaviruses cause warts.

Pathogenesis of Exanthems

• Muco-cutaneous manifestations of viral infections result from:
• Viral replication in the epidermis or mucous membranes
• Systemic infection
• Inflammatory response to a viral antigen
• Immunological response to a viral antigen

Measles – Clinical Manifestations

• Incubation period is about 10 days, being shorter in infants and longer (up to 3 weeks) in adults.
• Early symptoms include fever on day 1 (i.e., on the 10th day of infection), usually about 38.3°C + 3Cs, cough, coryza (runny nose), conjunctivitis (wet, red eye), and sore throat.
• Koplik's spots, pathognomonic for measles, appear after two days following fever:
• They are white to bluish spots (1 mm size) surrounded by erythema.
• They appear first on the buccal mucosa near the second lower molars, rapidly spreading to the entire buccal mucosa.

Measles - Rash and Immunity

• Rash: Maculopapular dusky red rashes appear after four days of fever (i.e., at the 14th day of infection).
• Rashes appear first behind the ears and then spread to the face, arm, and trunk, fading in the same order.
• Rashes are typically absent in HIV-infected people (due to reduced CMI response).
• Lifelong immunity is acquired after infection.
• Incubation period (10 days) → Fever (10th day) → Koplik's spot (12th day) → rash (14th day).

Measles Complications

• CNS complications are rare but most severe.
• Possible complications include post-measles encephalomyelitis and measles inclusion body encephalitis.
• Subacute sclerosing panencephalitis (SSPE) is a slowly progressive disease characterized by seizures and progressive deterioration of cognitive and motor functions.
• Occurrence is 1 in 300,000 measles cases. -SSPE typically occurs in persons infected with measles virus at < 2 years of age and develops after 7–10 years of initial infection.
• It is fatal within 1–3 years of onset, with a mortality rate of 10–20%.
• High titer antibody in CSF is diagnostic.

Rubella Virus

• It is a member of the family Togaviruses and subfamily Rubivirus.
• The virus has a small size, an icosahedral capsid surrounded by an envelope, a diameter of 60 to 65 nm, and a positive-sense, single-stranded RNA genome.

Congenital Rubella Syndrome

• Rubella causes a benign disease in adults and older children, but congenitally infected newborns may develop birth defects.

Parvovirus B19

• Transmitted through airborne exposure.
• It is seen in ages 18 – 35. Parvovirus produces a maculopapular rash during the second phase of the disease known as the fifth disease or erythema infectiosum.
• It is a self-limiting disease of children, and sometimes adults.
• The IP is 4 to 14 days and has a biphasic course.
• The first phase is an influenza-like disease beginning with fever, malaise, sore throat, myalgia, chills, and itching.

Erythema Infectiosum (Fifth Disease) – Second Phase

• Begins about 17 days after infection and presents with a characteristic erythematous rash on the face, appearing as if the person has been slapped.

Herpes Viruses

• The family Herpesviridae contains over 100 viruses of man and animals and possess common virion morphology, mode of replication, and the capacity to establish latent infections.
• There are six important human pathogens in the family: herpes simplex virus types 1 and 2, varicella-zoster, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 8.
• Herpesvirus has enveloped, icosahedral nucleocapsids, and a linear double-stranded DNA genome without a polymerase; it replicates in the nucleus and acquires the envelope by budding through the nuclear membrane.

Human Herpes Viruses and Their Genera

• HHV 1: Herpes simplex virus type 1, Genus: Simplexvirus
• HHV 2: Herpes simplex virus type 2, Genus: Simplexvirus
• HHV 3: Varicella-zoster virus, Genus: Varicellovirus
• HHV 4: Epstein Barr virus, Genus: Lymphocryptovirus
• HHV 5: Cytomegalovirus, Genus: Cytomegalovirus
• HHV 6: Human lymphotropic virus, Genus: Roseolovirus
• HHV 7: Human herpes 7, Genus: Roseolovirus
• HHV 8: Kaposi’s sarcoma-related virus, Genus: Lymphocryptovirus

Herpes Simplex – Transmission, Pathogenesis, and Pathology

• Herpes simplex is present in saliva, respiratory droplets, and exudates from lesions, and infection is acquired through contact with individuals shedding the virus.
• It enters the host through the mucous membrane of the oral mucosa, conjunctiva, or broken skin, multiplying to form vesicles at the site of entry.
• The virus then migrates up the neuron by retrograde axonal flow, establishing latency in the sensory ganglia, and the viral DNA integrates into the cellular chromosomes at the site of latency.

Herpes Zoster

• Latent infections are reactivated periodically due to trauma, stress, fever, sunlight, and depressed immunity; serious reactivated HSV infections often occur in AIDS patients.
• During reactivation, the virus travels down the axon to the peripheral site, multiplying there to produce lesions.
• Reactivated infections are generally less severe, more localized, and of shorter duration than primary infections
• HSV-1: Trigeminal Ganglion
• HSV-2: Lumbar and Sacral Ganglia
• HSV may spread to the brain and other vital organs due to immunosuppression.

HSV Infections - Complications

• Potential complications of HSV infections include keratitis, kerato-conjunctivitis, blindness, meningoencephalitis, sciatic nerve pain (radiculopathy), and cervical carcinoma.

Varicella Zoster Virus (Chickenpox)

• Usually lasts about 4 to 7 days
• A common sign is a rash that turns into itchy, fluid-filled blisters which eventually become scabs.
• It can be serious, even life-threatening, during pregnancy and in babies, adolescents, adults, and people with weakened immunity.
• Either body region may be infected by either subtype to produce clinically and histologically indistinguishable disease due to the 50% homology between the genomes of HSV-1 and -2.
• The lesions, though small, can be quite painful.

VZV Clinical Manifestations, Carriage Rate

• Chicken pox is a primary infection (varicella) in children
• "Shingles" is a reactivation of latent infection (Herpes zoster virus, or HZV) in adults.
• Carriage rate:
• HSV-1: 2 to 9% in asymptomatic adults
• HSV-2: 2-5% of men; approx 8% of women in STD clinics

Infectious Mononucleosis (Glandular Fever)

• Caused by the Epstein-Barr Virus
• Characterized by swollen tonsillar glands, skin rashes, and fever, and is a very common condition.
• Complicated by Burkitt's lymphoma, a rare benign tumor of the cervical lymph glands, and Kaposi's sarcoma.

Poxviruses

• Poxviruses belong to a family of large, genetically complex, linear double-stranded DNA viruses (with no obvious symmetry).
• Infections with most poxviruses are characterized by rash.
• Out of the eight genera of poxvirus, only four are of human concern: Orthopoxvirus, Parapoxvirus, Molluscipoxvirus and Yatapoxvirus
• Members of Orthopoxvirus include variola virus (highly virulent), vaccinia virus, monkey pox and cowpox virus

Poxviruses - Key Features

1. They are ovoid to brick-shaped, dsDNA viruses.
2. They can be seen by light microscope because of their large size.
3. They contain a DNA-dependent RNA polymerase (not found in other DNA viruses) to allow viral mRNA synthesis in the cytoplasm.
4. Unlike other DNA viruses, they replicate entirely in the cytoplasm of host cells

Smallpox

• It is an acute contagious disease caused by the variola virus, a member of the orthopoxvirus family.
• It was one of the most devastating diseases known to humanity and the first infectious disease to be declared eradicated from the earth in 1980.
• There is concern that the virus could be reintroduced as a biological weapon.
• Transmission occurs from person to person via infective droplets during close contact with infected people who have symptoms.

Smallpox: Clinical Features

• Incubation period: <12 days, Prodrome: 2 days
• High fever, chills, headache, severe back pain, abdominal pain
• Vomiting occurs
• Rash: Maculopapules, vesicles to pustules and scabs.
• In fulminant disease, death can occur before the rash

Diagnosis and Treatment of Viral Rash:

• Things to consider: Exposure history Rash location Absence or presence of fever Duration of symptoms