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Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023
| Contributor Information
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Image from Percinoto AC, Danelon M, Crivelini MM, Cunha RF, Percinoto C. BMC Res Notes. 2014 Jul 23;7:467. [Open access.] PMID: 25053204, PMCID: PMC4114792.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
Although condylomata acuminata, caused by human papillomavirus (HPV), are typically known as genital warts, the above image shows an oral outbreak of these lesions in a sexually abused child.
Viral infections can give rise to a variety of cutaneous and mucosal manifestations, from isolated lesions to generalized exanthems.
HPVs produce epithelial neoplasms of the skin and mucous membranes. More than 150 HPV types have been detected.[1] Before vaccination against HPV became available, about 340,000 to 360,000 people in the United States each year sought care for genital warts.[1-3] Approximately 90% of condylomata acuminata are related to HPV types 6 and 11,[3,4] which are not associated with a malignant potential.[3,4]
Image from Medscape.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
Common warts (verruca vulgaris) (arrow) are shown above.
Infections caused by HPVs are common and lead to the development of a wide variety of clinical manifestations involving the epidermal surfaces. Such manifestations include common warts, palmoplantar warts (verruca palmaris et plantaris), flat warts (verruca plana), oral warts, focal epithelial hyperplasia, and epidermodysplasia verruciformis.[5]
Image from Wikimedia Commons/James Heilman, MD.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
Herpetic whitlow (bracket) is an intensely painful infection of the hand that involves one or more fingers, with the terminal phalanx typically affected.[6] Human herpes virus type 1 (HHV-1), also known as herpes simplex virus type 1 (HSV-1), is the causative agent in approximately 60% of cases of herpetic whitlow, and HHV-2 (also known as HSV-2) causes the remaining 40%.[7]
Image courtesy of Medscape/Sheldon Mintz, DDS.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
Oral blisters (arrow) caused by HHV are shown.
Members of the HHV and HPV families are the most common causes of primary viral infections of the oral cavity.[8] (However, many other viral infections can affect this space, either as localized or as systemic infections.)
Recurrent HSV-1 is occasionally observed intraorally; it typically affects only keratinized tissue (mucosal tissue bound to bone) inside the oral cavity (eg, the gingiva or hard palate),[9,10] causing primary herpetic gingivostomatitis, or oral herpes. Because the vesicles often break quickly, the clinician may see small clustered ulcers.[10] HSV-1 becomes latent and may periodically recur as a common cold sore.[7,9,10]
There are eight known types of HHV.[7,10]
Image from Medscape.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
HSV-2 causes genital herpes (shown), and it occasionally gives rise to oral disease that is clinically similar to that of HSV-1 infection.[7,11,12] As with HSV-1, there is no cure, and treatment typically involves supportive care. However, antiviral drugs can make outbreaks less frequent and can help clear up symptoms more quickly.[13]
Image from Wikimedia Commons/Camiloaranzales.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
HHV-3, also known as varicella-zoster virus (VZV), causes the primary infection chickenpox (shown) and the secondary reactivation disease herpes zoster (shingles).[7,11] Chickenpox spots can be staged as blistering, bursting, drying, or crusting.[14] 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.[7,11]
Image from Wikimedia Commons/Fisle.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
Herpes zoster, or shingles (above), is the most common presentation of reactivated VZV. The majority of shingles cases occur in adults.[7,11] Patients typically report a prodromal illness of pain, pruritus, burning, and/or paresthesia. Over the next few days, erythematous macules and papules develop along a single dermatome (shown). These lesions then progress to vesicles that eventually crust and heal over.[7,11]
Herpes zoster ophthalmicus is a medical emergency.[7,11] This VZV infection involves the ophthalmic division of the trigeminal nerve and accounts for 10-25% of all cases of shingles.[15] The reactivated VZV may travel down the ophthalmic division to the nasociliary nerve (Hutchinson sign),[11] which innervates the tip of the nose and the surface of the globe of the eye.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
Ramsay Hunt syndrome, or herpes zoster oticus, is a reactivation of VZV that involves the facial nerve (cranial nerve VII).[10,16] Cranial nerves V, VI, VIII, and IX may also be involved.[16] Patients initially report pain deep within the ear that radiates to the pinna.[16] The infection then produces vesicles and ulcerations of the external ear (shown)[16,17] and of the ipsilateral anterior two thirds of the tongue and soft palate.[16]
Image from Wikimedia Commons/James Heilman, MD.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
HHV-4, also known as Epstein-Barr virus (EBV), causes infectious mononucleosis (shown), commonly referred to as "mono" or "kissing disease";[11,12] it is also implicated in various other disorders, including immunoproliferative diseases and nasopharyngeal carcinoma.[7,12] HHV-4 causes oral hairy leukoplakia in patients who are immunosuppressed.[7,12]
HHV-5, also known as cytomegalovirus (CMV), causes a primary infection of the salivary glands and other tissues and is believed to have a chronic form.[12] In immunocompromised individuals, CMV can produce chronic mucosal ulcerations as well as severe complications, such as hepatitis, leukopenia, pneumonitis, and death.[7,12]
Image from Medscape.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
HHV-6, which can produce acute infection in CD4+ T lymphocytes,[18] causes roseola infantum (sixth disease) (shown), a febrile illness that affects young children and may manifest with a macular or maculopapular rash.[7,18] 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.[19]
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.[18]
Image from the National Cancer Institute (NCI).
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
HHV-8 is associated with Kaposi sarcoma (which is characterized by violaceous to brown patches, plaques, and nodules)[20,21](shown) and with body-cavity lymphomas and Castleman disease.[20,22] HHV-8 genomic sequences have been identified by polymerase chain reaction (PCR) assay in all types of Kaposi sarcoma (including epidemic and endemic forms), strongly suggesting a causative role for this DNA virus.[21,22] HHV-8 is transmitted sexually and by contact with saliva.[20,22]
Image from the CDC.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
The above image demonstrates the morbilliform eruption found in rubella (German measles).
Rubella is caused by the rubella virus, a member of the genus Rubivirus, of the family Togaviridae.[23,24] Clinical manifestations and severity of illness vary with age, although 20-50% of infected individuals are asymptomatic.[23,25] Infection in younger children is characterized by mild constitutional symptoms, morbilliform eruption, and cervical, postauricular, and suboccipital adenopathy.[23] In older children, adolescents, and adults, rubella may be complicated by arthralgias, arthritis, and thrombocytopenic purpura.[25] Petechial lesions known as the Forchheimer sign (reddish maculopapular eruption on the soft palate)[10,23] are observed in approximately 20% of patients with German measles.
Image from Wikimedia Commons/Andrew Kerr.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
The "slapped-cheek" and body rashes of fifth disease are shown.
Fifth disease (erythema infectiosum) is caused by parvovirus B19. Its name was derived from the fact that "it was fifth in a list of historical classifications of common skin rash illnesses in children."[26] Patients with this infection generally present with symptoms that include a low-grade fever, malaise, a slapped-cheek rash, and a rash over the whole body.[11] Although fifth disease is relatively mild in most children, youngsters with immunodeficiency or certain blood disorders may become very ill.[27] Parvovirus B19 can temporarily decrease or halt the body's production of red blood cells, causing anemia.[11] Infection in adolescents and adults often presents as arthralgias or arthritis rather than a rash.[11,27]
Image from the CDC.
Cutaneous and Mucosal Manifestations of Viral Diseases
Mark P Brady, PA-C | March 6, 2023 | Contributor Information
The intraoral lesions shown (arrow) are Koplik spots, which are a pathognomonic enanthem of measles.[28-30] 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.[30] It can affect people of all ages, despite being considered primarily a childhood illness.
Measles is marked by a prodromal fever, cough, coryza, and conjunctivitis, followed by an erythematous maculopapular rash[28-30] on the third to seventh day of infection; the rash spreads from the head to the trunk and extremities.[29,30] Infection confers lifelong immunity.[31]
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 6, 2023 | Contributor Information
The vesicle shown is surrounded by an erythematous halo. It is caused by the nonpolio enterovirus coxsackie A16, which is the etiologic agent involved in most cases of hand-foot-and-mouth disease (HFMD).[11,32] HFMD is an acute viral illness that presents as a vesicular eruption in the mouth but can also affect the hands, feet, buttocks, and genitalia.[5,32,33]
The mucosal lesions of HFMD rapidly progress from erythematous macules 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 oral lesions appear.[5,32] 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.[33,34]
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 6, 2023 | Contributor Information
Molluscum contagiosum is a benign viral disease of the skin[11,35] that is caused by a member of the poxvirus group, the molluscum contagiosum virus.[11] Molluscum contagiosum usually presents as a single or multiple (usually no more than 20) discrete, painless, flesh-colored papule or papules that classically have a central umbilication (shown).[11,34-36] 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 occur in the groin and genitalia.[11,34,36]
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Contributor Information
Author
Mark P Brady, PA-C
Adjunct Faculty and Preceptor
Physician Assistant Program
University of New England;
Physician Assistant
Department of Emergency Medicine
Cambridge Hospital, Cambridge Health Alliance
Cambridge, MA
Disclosure: Mark P. Brady, PA-C, has disclosed no relevant financial relationships.
Reviewer
Brett Sloan, MD, FAAD
Professor of Dermatology
Dermatology Residency Program Director
University of Connecticut School of Medicine;
Editor-in-Chief Journal of the American Academy of Dermatology Case Reports
Disclosure: Brett Sloan, MD, FAAD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Journal of the American Academy of Dermatology; UpToDate; Medical Review Institute of America.
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References
Human papillomavirus (HPV). Centers for Disease Control and Prevention. July 23, 2021. Available at: https://www.cdc.gov/hpv/. Accessed February 22, 2023.
Genital HPV infection - Basic Fact Sheet. Centers for Disease Control and Prevention. April 12, 2022. Available at: https://www.cdc.gov/std/hpv/STDFact-HPV.htm. Accessed February 22, 2023.
Hawkins MG, Winder DM, Ball SL, et al. Detection of specific HPV subtypes responsible for the pathogenesis of condylomata acuminata. Virol J. 2013 May 1;10:137. [PMID: 23634957]
Human Papillomavirus (HPV). Centers for Disease Control and Prevention. July 22, 2021. Available at: https://www.cdc.gov/std/hpv/default.htm. Accessed February 22, 2023.
Human papillomavirus. Sharland M, ed. Manual of Childhood Infections: The Blue Book. 3rd ed. Oxford University Press; 2011: 587-94.
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Neville BW, Damm DD, Allen CM, Chi AC. Viral infections. Oral and Maxillofacial Pathology. 4th ed. Elsevier Saunders; 2016: 218-58.
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Lynch DP. Oral manifestations of viral diseases. Tyring SK, ed. Mucosal Immunology and Virology. Springer-Verlag; 2006: Chapter 5.
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Cohen JI. Human herpesvirus types 6 and 7 (exanthema subitum). Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Elsevier Saunders; 2015: Chapter 142.
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Gershon AA. Measles virus (rubeola). Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Elsevier-Saunders; 2015: Chapter 162.
Muller CP, Kremer J. Measles (rubeola). Kellerman BI, ed. Conn's Current Therapy 2015: Expert Consult. Elsevier Saunders; 2015: 153.
Measles (Rubeola). Centers for Disease Control and Prevention. November 5, 2020. Available at: https://www.cdc.gov/measles/index.html. Accessed February 22, 2023.
Maldonado YA. Rubeola virus (measles and subacute sclerosing panencephalitis). Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Disease. 4th ed. Elsevier Saunders; 2012: Chapter 227.
Hand, Foot, and Mouth Disease (HFMD). Centers for Disease Control and Prevention. February 2, 2021. Available at: https://www.cdc.gov/hand-foot-mouth/. Accessed February 22, 2023.
Treat J. Vesicles and bullae. Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Disease. 4th ed. Elsevier Saunders; 2012: 440.
Thomas J, Kumar P. Infections and infestations. Clinical Pediatric Dermatology. Jaypee Brothers; 2013: 47-8, 52-5.
Leung AKC. The natural history of molluscum contagiosum in children. Lancet Infect Dis. 2015 Feb;15(2):136-7. [PMID: 25541477]
Lauren CT, Garzon MC. Papules, nodules, and ulcers. Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Disease. 4th ed. Elsevier Saunders; 2012: 450-3.
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