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Image courtesy of Medscape/Rose Yin Geist, DDS.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Viral infections can cause a variety of cutaneous and mucosal manifestations, from isolated lesions to generalized exanthems.

What is the viral etiology of the lesion shown above, on the lateral border of the tongue?

  1. Coxsackie A virus, type 16 (A16)
  2. Human herpesvirus (HHV)
  3. Human papillomavirus (HPV)
  4. Cytomegalovirus (CMV)
Image from the Centers for Disease Control and Prevention (CDC).

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Answer: C. Human papillomavirus (HPV).

HPVs produce epithelial neoplasms of the skin and mucous membranes.[1] More than 150 HPV types have been detected.[2] HPVs also cause genital warts (condylomata acuminata) (shown),[1-4] which affect about 360,000 people in the United States each year.[3] Approximately 90% of condylomata acuminata are related to HPV types 6 and 11,[4,5] which are not associated with a malignant potential.[1,4,5] HPV vaccination against oncogenic HPV types is recommended for boys and girls and for young people before they begin sexual activity, with the aim of reducing the risk of oral and anogenital cancers in males and females.[2,3,5] Vaccination is also recommended through age 26 years for gay men, bisexual men, other men who have sex with men, transgender people, and immunocompromised persons (including those with HIV infection) not adequately vaccinated previously.[6]

Image courtesy of Medscape.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Infections caused by HPVs are common and lead to the development of a wide variety of clinical manifestations that involve the epidermal surfaces. Such manifestations include common warts (verruca vulgaris) (arrow), palmoplantar warts (verruca palmaris et plantaris), flat warts (verruca plana), oral warts, focal epithelial hyperplasia, and epidermodysplasia verruciformis.[7]

Image courtesy of Medscape.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

What is the name of this lesion (arrow)? Which virus is responsible for the lesion?

Image from Wikimedia Commons/James Heilman, MD.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Answer: Herpetic whitlow.

Herpetic whitlow (bracket) is an intensely painful infection of the hand that involves one or more fingers, typically affecting the terminal phalanx.[8] Herpes simplex virus (HSV)–1 is the causative agent in approximately 60% of cases of herpetic whitlow, and HSV-2 causes the remaining 40%.[9]

Image courtesy of Medscape/Sheldon Mintz, DDS.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Members of the HHV and HPV families are the most common causes of primary viral infections of the oral cavity.[10] However, many other viral infections can affect the oral cavity, either as localized or as systemic infections.

Recurrent HHV type 1, or HSV-1, is occasionally observed intraorally, typically affecting only keratinized tissues (mucosal tissue bound to bone) inside the oral cavity (eg, gingiva, hard palate).[11,12] Vesicles (arrow) often break quickly, so the clinician may observe small clustered ulcers. The lesions shown are actually blisters.[12]

How many serotypes of HHV are currently known?

Image of HSV-1 lesions (cold sores) from the CDC/Robert E. Sumpter.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Answer: Eight.

There are eight known types of HHV.[9,12] HHV-1 causes primary herpetic gingivostomatitis, or oral herpes. This virus becomes latent and may periodically recur as a common cold sore.[9,11,12]

Image courtesy of Medscape.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

HHV-2, also known as HSV-2, causes genital herpes (shown), and it occasionally causes oral disease that is clinically similar to that of HHV-1 infection.[9,13,14] As with HSV-1, there is no cure, and treatment typically involves supportive care. However, antiviral drugs can make outbreaks less frequent and help clear up symptoms more quickly.[15]

Image from Wikimedia Commons/Camiloaranzales.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

HHV-3, also known as varicella-zoster virus (VZV), causes the primary infection chickenpox and the secondary reactivation disease herpes zoster (shingles).[9,13] Chickenpox spots can be staged as blistering, bursting, drying, and crusting.[16] Chickenpox is uncommon, because of the use of the VZV vaccine in the pediatric population. Adults who have had chickenpox as a child are at risk for developing shingles later in life from reactivation of the virus.[9,13]

Image from Wikimedia Commons/Fisle.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Herpes zoster, or shingles, is the most common presentation of reactivated VZV. The majority of cases of shingles occur in adults.[9,13] Patients typically report a prodromal illness of pain, pruritus, burning, and/or paresthesias. Over the next few days, erythematous macules and papules develop along a single dermatome (shown). The macules and papules then progress to vesicles that eventually crust and heal over.[9,13]

Image courtesy of Medscape/JS Huff.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Herpes zoster ophthalmicus (shown) is a medical emergency.[9,13] This VZV infection involves the ophthalmic division of the trigeminal nerve and accounts for 10-25% of all cases of shingles.[17] The reactivated VZV may travel down the ophthalmic division to the nasociliary nerve (Hutchinson sign),[13] which innervates the tip of the nose and the surface of the globe of the eye.

Image courtesy of Medscape/Manolette Roque, MD, Ophthalmic Consultants Philippines Co, Eye Republic Ophthalmology Clinic.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Ramsay Hunt syndrome, or herpes zoster oticus, is a reactivation of VZV that involves the facial nerve.[12,18] Cranial nerves V, VI, VIII, and IX may also be involved.[18] Patients initially report pain deep within the ear that radiates to the pinna.[18] The infection then produces vesicles and ulcerations of the external ear (shown)[18,19] and of the ipsilateral anterior two thirds of the tongue and soft palate.[18]

Image from Wikimedia Commons/James Heilman, MD.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

HHV-4, also known as Epstein-Barr virus (EBV), causes infectious mononucleosis (shown), commonly referred to as "mono" or "kissing disease"[13,14]; it is also implicated in various other diseases, including immunoproliferative disorders and nasopharyngeal carcinoma.[9,14] HHV-4 causes oral hairy leukoplakia in patients who are immunosuppressed.[9,14]

HHV-5, also known as CMV, causes a primary infection of the salivary glands and other tissues and is believed to have a chronic form.[14] In immunocompromised individuals, CMV can cause chronic mucosal ulcerations as well as severe complications, such as hepatitis, leukopenia, pneumonitis, and death.[9,14]

Image courtesy of Medscape.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

HHV-6, which can produce acute infection in CD4+ T lymphocytes,[20] causes roseola infantum (sixth disease) (shown), a febrile illness that affects young children and may manifest with a macular or maculopapular rash.[9,20] It is believed to persist chronically in salivary gland tissue in some hosts. Oral shedding is the probable route of disease transmission.

Primary HHV-6B infection usually occurs in infants and is the most common cause of fever-induced seizures in children aged 6-24 months.[21]

HHV-7 has been isolated from the saliva of healthy adults, has been detected in breast milk, and has been implicated as another cause of roseola infantum and febrile seizures in children.[20]

Image from the National Cancer Institute (NCI).

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

HHV-8 is associated with Kaposi sarcoma (violaceous to brown patches, plaques, and nodules)[22,23] (shown) and with body-cavity lymphomas and Castleman disease.[22,24] HHV-8 genomic sequences have been identified by polymerase chain reaction assay in all types of Kaposi sarcoma (including epidemic and endemic forms), strongly suggesting a causative role for this DNA virus.[23,24] However, although HHV-8 infection is necessary, it alone is not sufficient for the development of Kaposi sarcoma.[23] This virus is transmitted sexually and by contact with saliva.[22,24]

When was the last reported case of smallpox in the United States?

  1. 1949
  2. 1961
  3. 1977
  4. 1993
Image courtesy of Medscape/World Health Organization (WHO).

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Answer: A. 1949.

The last case of smallpox in the United States was in 1949.[25] The last naturally occurring case in the world was in Somalia in 1977.[25,26] The smallpox virus is transmitted mainly through the airborne route and adheres by means of droplet spread of viral particles onto the oropharyngeal and respiratory tract mucosal surfaces.[26,27] This transmission results from extended periods of close contact (eg, face-to-face within 6 feet, household contact) and via contaminated objects such as clothing and bedding.[25-27]

These images show the smallpox rash at days 3, 5, and 7 of evolution. Lesions are denser on the face and extremities than on the trunk. Their monomorphous appearance is noteworthy.[26,27] Lesions also appear on the palms of the hands and have a similar appearance.[25-27]

Image from Wikimedia Commons/Steffen Bernard.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Petechial lesions known as the Forchheimer sign[12,28] are observed in approximately 20% of patients with which viral illness?[12]

  1. Rubeola
  2. Coxsackie virus
  3. Rubella
  4. HPV
  5. HHV
Image from the CDC.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Answer: C. Rubella.

Rubella (German measles) is caused by the rubella virus, a member of the genus Rubivirus of the family Togaviridae.[28,29] Clinical manifestations and severity of illness vary with age, although 20-50% of infected individuals are asymptomatic.[28,30] Infection in younger children is characterized by mild constitutional symptoms, maculopapular rash (shown), and cervical, postauricular, and suboccipital adenopathy.[28] Conversely, in older children, adolescents, and adults, rubella may be complicated by arthralgias, arthritis, and thrombocytopenic purpura.[30]

With which viral disease is parvovirus B19 associated?

Image from Wikimedia Commons/Andrew Kerr.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Answer: Fifth disease.

Fifth disease (erythema infectiosum) received its odd name owing to the fact that in the prevaccination era, it was frequently the fifth disease that a child contracted. Patients with this parvovirus B19 infection generally present with symptoms that include a low-grade fever, malaise, a "slapped-cheek" rash, and a rash over the whole body (shown).[13] Although fifth disease is relatively mild in most children, some children with immunodeficiency or certain blood disorders may become very ill.[31] Parvovirus B19 can temporarily decrease or halt the body's production of red blood cells, causing anemia.[13] Infection in adolescents and adults often presents as arthralgias or arthritis rather than a rash.[13,31]

Image from the CDC.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

What is the name of the intraoral lesion shown (arrow)? Of which viral illness is this lesion a pathognomonic enanthem?

Image from the CDC.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Answer: Koplik spots are a pathognomonic enanthem of measles.[32-34]

Also known as rubeola, measles is one of the most contagious infectious diseases, with at least a 90% secondary infection rate in susceptible domestic contacts.[34] It can affect people of all ages, despite being considered primarily a childhood illness.

Measles is marked by prodromal fever, cough, coryza, and conjunctivitis, followed by an erythematous maculopapular rash[32-34] (shown) on the third to seventh day of infection that spreads from the head to the trunk and extremities.[33,34] Infection confers lifelong immunity.[35] From January to September 2019, 1249 US measles cases were reported, the highest annual number since 1992.[36] Eighty-nine percent of measles patients were unvaccinated or had an unknown vaccination status, and 10% were hospitalized. Eighty-six percent of cases were associated with outbreaks in underimmunized, close-knit communities, including two outbreaks in New York Orthodox Jewish communities that threatened measles elimination status in the United States.[36]

Image from Sarma N, Sarkar A, Mukherjee A, Ghosh A, Dhar S, Malakar R. Indian J Dermatol. 2009;54(1):26-30. [Open access.] PMID: 20049265, PMCID: PMC2800866.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

The vesicle shown is surrounded by an erythematous halo. What is the viral etiology of this cutaneous lesion?

Image from Yin XG, Yi HX, Shu J, Wang XJ, Wu XJ, Yu LH. BMC Infect Dis. 2014;14:251.[Open access.] PMID: 24885052,PMCID: PMC4026826.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Answer: Hand-foot-and-mouth disease (HFMD).

The non–polio enterovirus coxsackie A16 is the etiologic agent involved in most cases of HFMD,[13,37] an acute viral illness that presents as a vesicular eruption in the mouth but can affect the hands, feet, buttocks, and/or genitalia.[7,37,38] The mucosal lesions rapidly progress to vesicles that erode and become surrounded by an erythematous halo. Skin lesions, which present as tender macules or vesicles on an erythematous base, develop in approximately 75% of patients with HFMD, usually 1-2 days after the oral lesions appear.[7,37] Palmar and plantar lesions tend to be elliptical, have an erythematous halo, and have the long axis of the lesion oriented along the skin lines.[38,39]

Image from Sarma N, Sarkar A, Mukherjee A, Ghosh A, Dhar S, Malakar R. Indian J Dermatol. 2009;54(1):26-30. [Open access.] PMID: 20049265, PMCID: PMC2800866.

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Oral lesions of HFMD may involve the palate, buccal mucosa, gingiva, and tongue.[7,37,39] They begin as erythematous macules that evolve into 2- to 3-mm vesicles on an erythematous base.[39] The vesicles are rarely observed because they easily rupture and rapidly become ulcerated (shown).[38,39] The lesions are painful and may interfere with eating.[37] In 44% of cases, the tongue is affected, with tenderness and the presence of ulcers and edema.[39]

Image from Wikimedia Commons/E van Herk (left); CDC/Dave Bray, MD, Walter Reed Army Medical Center (right).

Cutaneous and Mucosal Manifestations of Viral Diseases

Mark P Brady, PA-C | March 4, 2020 | Contributor Information

Molluscum contagiosum is a benign viral disease of the skin[13,40] that is caused by a member of the poxvirus group, the molluscum contagiosum virus.[13] Molluscum contagiosum usually presents as single or multiple (ie, usually no more than 20) discrete, painless, flesh-colored papules that classically have a central umbilication (shown).[13,39-41] The lesions are usually smaller than 6 mm, but they can grow as large as 3 cm. They may be located anywhere, but in children, they have a predilection for the face, trunk, and extremities, whereas in adults, the lesions tend to be located in the groin and genitalia.[13,39,41]

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Hand-foot-and-mouth disease (HFMD) is a viral illness with a distinct clinical presentation of oral and characteristic distal extremity lesions. Most commonly, the etiologic agents are coxsackieviruses, members of the Picornaviridae family.Diseases/Conditions, June 2018
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