Epidermodysplasia verruciformis (also called
Lewandowsky-Lutz dysplasia or
Lutz-Lewandowsky epidermodysplasia verruciformis) is an extremely rare autosomal recessive genetic
hereditary skin disorderGenodermatoses are inherited genetic skin conditions often grouped into three categories: chromosomal, single gene, and polygenetic....
associated with a high risk of
carcinomaA carcinoma is any malignant cancer that arises from epithelial cells. Carcinomas invade surrounding tissues and organs and may metastasize, or spread, to lymph nodes and other sites....
of the skin. It is characterized by abnormal susceptibility to
human papillomavirusA human papillomavirus is a papillomavirus that infects the epidermis and mucous membranes of humans. HPV can lead to cancers of the cervix, vulva, vagina, and anus in women. In men, it can lead to cancers of the anus and penis....
es (HPVs) of the skin. The resulting uncontrolled HPV infections result in the growth of scaly
maculeA macule is a change in epidermis color, without elevation or depression and, therefore, nonpalpable, well or ill-defined, variously sized but, by convention, less than ten milimeters in diameter at the widest point.[With regard to the quote "...by convention, less than...]
s and
papuleA papule is a circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to 1 cm.[With regard to the quote "...varying in size from a pinhead to 1cm," depending on which text is referenced, some authors state the cutoff between a...]
s, particularly on the hands and feet.
Epidermodysplasia verruciformis (also called
Lewandowsky-Lutz dysplasia or
Lutz-Lewandowsky epidermodysplasia verruciformis) is an extremely rare autosomal recessive genetic
hereditary skin disorderGenodermatoses are inherited genetic skin conditions often grouped into three categories: chromosomal, single gene, and polygenetic....
associated with a high risk of
carcinomaA carcinoma is any malignant cancer that arises from epithelial cells. Carcinomas invade surrounding tissues and organs and may metastasize, or spread, to lymph nodes and other sites....
of the skin. It is characterized by abnormal susceptibility to
human papillomavirusA human papillomavirus is a papillomavirus that infects the epidermis and mucous membranes of humans. HPV can lead to cancers of the cervix, vulva, vagina, and anus in women. In men, it can lead to cancers of the anus and penis....
es (HPVs) of the skin. The resulting uncontrolled HPV infections result in the growth of scaly
maculeA macule is a change in epidermis color, without elevation or depression and, therefore, nonpalpable, well or ill-defined, variously sized but, by convention, less than ten milimeters in diameter at the widest point.[With regard to the quote "...by convention, less than...]
s and
papuleA papule is a circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to 1 cm.[With regard to the quote "...varying in size from a pinhead to 1cm," depending on which text is referenced, some authors state the cutoff between a...]
s, particularly on the hands and feet. It is typically associated with HPV types 5 and 8, which are found in about 80% of the normal population as asymptomatic infections, although other types may also contribute.
The condition usually has an onset of between the ages of 1–20, but can occasionally present in middle-age. It is named after the physicians who first documented it,
Felix LewandowskyFelix Lewandowsky was a German dermatologist who was a native of Hamburg.In 1902 he earned his doctorate at Strassburg, and from 1903 until 1907 he worked at the dermatological clinic in Bern where he was an assistant to Josef Jadassohn . Afterwards he returned to Hamburg where he worked in...
and Wilhelm Lutz.
Genetic cause
The cause of the condition is an inactivating mutation in either the EVER1 or EVER2 genes, which are located adjacent to one another on chromosome 17. The precise function of these genes is not yet fully understood, but they play a role in regulating the distribution of zinc in the cell nucleus. It has been shown that zinc is a necessary cofactor for many viral proteins, and that the activity of EVER1/EVER2 complex appears to restrict the access of viral proteins to cellular zinc stores, limiting their growth.
Diagnosis
Clinical diagnostic features are lifelong eruption of pityriasis versicolor-like macules, flat wart-like papules and development of cutaneous carcinomas.
Patients present with flat, slightly scaly, red-brown macules on the face, neck and body, or verruca-like papillomatous lesions, seborrheic keratosis-like lesions, and pinkish-red plane papules on the hands, upper and lower extremities, and face. The benign form of EV presents with only flat, wart-like lesions over the body, whereas the malignant form shows a higher rate of polymorphic skin lesions and development of multiple
cutaneousThe skin is the outer covering of the body. In humans, it is the largest organ of the integumentary system made up of multiple layers of mesodermal tissue, and guards the underlying muscles, bones, ligaments and internal organs. Skin of a different nature exists in amphibians, reptiles, birds...
tumorA tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells . Tumor is not synonymous with cancer. A tumor can be benign, pre-malignant or malignant, whereas cancer is by definition malignant....
s.
Generally cutaneous lesions are disseminated over the body, but there are some cases with only a few lesions which are limited to one extremity.
Treatment
A totally effective treatment method against EV has not yet been found. Several treatments have been suggested, and
acitretinAcitretin is a second generation retinoid. It is taken orally, and is typically used for psoriasis.It is a metabolite of etretinate, which was used prior to the introduction of acitretin. Etretinate was discontinued because it had a narrow therapeutic index as well as a long elimination...
0.5–1 mg/day for 6 months’ duration is the most effective treatment owing to antiproliferative and differentiation-inducing effects.
InterferonInterferons are natural cell-signaling proteins produced by the cells of the immune system of most vertebrates in response to challenges such as viruses, parasites and tumor cells. They belong to the large class of glycoproteins known as cytokines and are produced by a wide variety of cells in...
s can also be used effectively together with
retinoidThe retinoids are a class of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth....
s.
CimetidineCimetidine is a histamine H
2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers...
was reported to be effective because of its depressing
mitogenA mitogen is a chemical substance that encourages a cell to commence cell division, triggering mitosis. A mitogen is usually some form of a protein....
-induced
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.By their appearance under the light microscope, there are two broad categories of lymphocytes, namely the large granular lymphocytes and the small lymphocytes. Functionally distinct subsets of lymphocytes correlate with...
proliferation and
Regulatory T cellRegulatory T cells are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens. The existence of a dedicated population of suppressive T cells was the subject of significant...
activity features. A report by Oliveira
et al. showed that cimetidine was ineffective. Hayashi et al. applied topical
calcipotriolCalcipotriol or calcipotriene is a synthetic derivative of calcitriol or Vitamin D. It is used in the treatment of psoriasis, marketed under the trade name Dovonex or Daivonex.-Mechanism:...
to a patient with a successful result.
As mentioned, various treatment methods are offered against EV; however, most importantly, education of the patient, early diagnosis and excision of the tumoral lesions take preference to prevent the development of cutaneous tumors.
Notable cases
In March 2007, a Romanian man named Ion Toader was diagnosed with this condition. The man, a patient of dermatologist Carmen Madeleine Curea, his pictures appeared on numerous blogs and Romanian press sources. Curea works out of Spitalului Clinic Colentina in
BucharestBucharest is the capital city, industrial and financial centre of Romania. It is the largest city in Romania, located in the southeast of the country, at , and lies on the banks of the Dâmboviţa River....
,
RomaniaRomania is a country located in Southeastern and Central Europe, North of the Balkan Peninsula, on the Lower Danube, within and outside the Carpathian arch, bordering on the Black Sea. Almost all of the Danube Delta is located within its territory...
. Stephen Stone, past president of the
American Academy of DermatologyThe American Academy of Dermatology is the largest organization of dermatologists in the world. It was founded in 1938 and represents 15,000 dermatologists in the United States and Canada. The Academy grants Fellowships and Associate Memberships, as well as Fellowships for Nonresidents of the USA...
, confirms this is Lewandowsky-Lutz.
In November 2007, a new video of a 34-year-old Indonesian man named Dede Koswara with a similar disease appeared on the internet. His story has appeared in the
Discovery ChannelDiscovery Channel is an American satellite and cable TV channel , founded by John Hendricks and distributed by Discovery Communications. It provides documentary programming focused primarily on popular science, technology, and history...
and
TLCTLC is an American cable TV network which carries a variety of informational and reality-based programming. Since 1991 TLC has been owned by Discovery Communications, the same company that operates the Discovery Channel, Animal Planet and The Science Channel, as well as other learning-themed...
series "My Shocking Story" ("Extraordinary People" on UK's Five) in the episode "Half Man Half Tree". And then on August 12, 2008, Dede Koswara's story was the subject of an ABC's Medical Mystery episode entitled "Tree Man".
On , Dede returned home following surgery to remove of warts from his body. The surgery consisted of four steps:
- Removal of the thick carpet of warts and massive horns on his hand. A heavy duty power saw had to be used.
- Removal of the smaller warts on his head, torso, and feet.
- Covering of the hands with grafted skin.
In all, 95% of the warts were removed. The surgery was documented by the Discovery Channel and TLC in the episode "Treeman: Search for the Cure." However, his warts have returned and it appears he will need two surgeries a year for the rest of his life to keep them at bay.
External links
- Romanian case
- Indonesian case