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Disease Profile

Epidermodysplasia verruciformis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

All ages

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ICD-10

B07

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Lewandowsky-Lutz syndrome; Lutz-Lewandowsky epidermodysplasia verruciformis

Categories

Congenital and Genetic Diseases; Immune System Diseases; Skin Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 302

Definition
Epidermodysplasia verruciformis (EV) is a rare inherited genodermatosis characterized by chronic infection with human papillomavirus (HPV) leading to polymorphous cutaneous lesions and high risk of developing non melanoma skin cancer.

Epidemiology
The exact prevalence of EV is unknown; more than 200 cases have been reported in the literature so far.

Clinical description
The disease usually manifests during infancy (7.5% of cases), childhood (61.5% of cases) or puberty (22% of cases) with a progressive development of hyperpigmented or hypopigmented flat wart-like papules, irregular reddish brown plaques, seborrheic keratosis-like lesions and pityriasis versicolor-like macules on the trunk, neck, face, dorsal hands and feet (sun-exposed skin). Various HPV subtypes (HPV5 and HPV8 are found in 80% of cases) can be detected in the cutaneous lesions. Thirty to 60% of patients develop non-melanoma skin cancers, especially squamous cell carcinomas (SCC), during the fourth or fifth decades of life, mainly on sun-exposed areas. Black-skinned patients have a much lower incidence of skin cancer. Most SCC remain local; metastases are uncommon.

Etiology
EV can be caused by loss-of-function mutations in either of the 2 adjacent genes EVER1/TMC6 or EVER2/TMC8 (17q25.3) coding for membrane proteins that form a complex with the Zinc transporter protein ZnT-1 in the endoplasmic reticulum (ER) membrane of keratinocytes. The mutations in these genes lead to susceptibility to infection with specific HPV subtypes belonging to the beta genus, including HPV5, 8, 9, 12, 14, 15, 17, 19-25, 36-38, 47 and 49, which are ubiquitous and harmless to healthy individuals.

Diagnostic methods
Diagnosis is based on clinical and histological findings. Skin biopsy shows verruca plana-like lesions with mild hyperkeratosis, hypergranulosis and acanthosis of the epidermis. Keratinocytes of the upper epidermal layers are enlarged with perinuclear vacuolization and a typical blue-gray pallor. HPVs can be detected in keratinocytes using in situ hybridization or immunohistochemistry with anti-HPV antibodies.

Differential diagnosis
Differential diagnosis includes squamous cell carcinoma, acrokeratosis verruciformis (see these terms), tinea versicolor, and generalized verrucosis of other origin. In addition, an acquired epidermodysplasia verruciformis-like syndrome has been described in patients with impaired cell-mediated immunity, mainly HIV-infected subjects.

Genetic counseling
In most cases, transmission is autosomal recessive but sex-linked and autosomal dominant inheritance patterns have also been reported.

Management and treatment
Although permanent cure of EV cannot be achieved by any therapy at present, described treatment modalities include cryotherapy, topical imiquimod and 5-fluorouracil, systemic retinoids, interferon alpha, and 5-aminolevulinic acid photodynamic therapy. Surgical excision is the treatment of choice for SCC. Preventive measures, in particular sun exposure avoidance and photoprotection, are crucial for proper management.

Prognosis
Prognosis is favorable since skin tumors appear progressively and metastases are uncommon.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Papule
0200034
Pustule
Pimple
0200039
Recurrent skin infections
Skin infections, recurrent
0001581
Seborrheic dermatitis
0001051
Skin plaque
0200035
Verrucae
Warts
0200043
30%-79% of people have these symptoms
Hypopigmented skin patches
Patchy loss of skin color
0001053
Multiple cafe-au-lait spots
0007565
5%-29% of people have these symptoms
Squamous cell carcinoma
0002860
Telangiectasia of the skin
0100585
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

0001939
Autosomal recessive inheritance
0000007
Basal cell carcinoma
0002671

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Epidermodysplasia verruciformis. Click on the link to view a sample search on this topic.