Epidermodysplasia verruciformis
Encyclopedia
Epidermodysplasia verruciformis (also called Lewandowsky-Lutz dysplasia or Lutz-Lewandowsky epidermodysplasia verruciformis) is an extremely rare autosomal recessive genetic hereditary skin disorder
associated with a high risk of carcinoma
of the skin. It is characterized by abnormal susceptibility to human papillomavirus
es (HPVs) of the skin. The resulting uncontrolled HPV infections result in the growth of scaly macules and papule
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 Lewandowsky
and Wilhelm Lutz.
Patients present with flat, slightly scaly, red-brown macules on the face, neck and body, recurring especially around the penial area, 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 cutaneous
tumor
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.
0.5–1 mg/day for 6 months’ duration is the most effective treatment owing to antiproliferative and differentiation-inducing effects.
Interferon
s can also be used effectively together with retinoid
s.
Cimetidine
was reported to be effective because of its depressing mitogen
-induced lymphocyte
proliferation and Regulatory T cell
activity features. A report by Oliveira et al. showed that cimetidine was ineffective. Hayashi et al. applied topical calcipotriol
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.
, Romania
. Stephen Stone, past president of the American Academy of Dermatology
, 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 Channel
and TLC
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 26 August 2008, Dede returned home following surgery to remove 6 kg (13 lb) of warts from his body. The surgery consisted of three steps:
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. The Discovery Channel funded a blood analysis and found he lacked an immune system antigen to fight yeast infection. He was offered to have more tests run to determine whether it is treatable, and the doctor was fairly optimistic, but he refused the treatment.
In 2009 the Discovery Channel episode "Treeman Meets Treeman" reported on another Indonesian man, from the same region as Dede, who also has the disease and was given a similar treatment for it. Thus far his treatment seems to have worked better.
According to The Jakarta Post, Dede underwent the first of a series of new surgical procedures to remove the regrown warts in the spring of 2011. Surgery has however proven to be a temporary solution for Dede as the warts continue to reemerge. He has thus undergone three surgical operations since his major surgery in 2008, which was covered by the Discovery channel. At the end of December 2010, two doctors from Japan, affiliated with the Japanese Society for Complementary and Alternative Medicine came and brought Dede alternative medicine in powder form, made from coix seeds. The medicine is still undergoing a lab test.
in 2009.
Additionally, a similar case was featured on Grey's Anatomy season 7
in 2010.
Genodermatosis
Genodermatoses are inherited genetic skin conditions often grouped into three categories: chromosomal, single gene, and polygenetic....
associated with a high risk of carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...
of the skin. It is characterized by abnormal susceptibility to human papillomavirus
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
es (HPVs) of the skin. The resulting uncontrolled HPV infections result in the growth of scaly macules and papule
Papule
A 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 papule and a plaque as 0.5cm,...
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 Lewandowsky
Felix Lewandowsky
Felix Lewandowsky was a German dermatologist who was a native of Hamburg.-Biography:He was born on October 1, 1879 and in 1902 he earned his doctorate at Strassburg. From 1903 until 1907 he worked at the dermatological clinic in Bern where he was an assistant to Josef Jadassohn...
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, recurring especially around the penial area, 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 cutaneous
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
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
Acitretin is a second generation retinoid. It is taken orally, and is typically used for psoriasis....
0.5–1 mg/day for 6 months’ duration is the most effective treatment owing to antiproliferative and differentiation-inducing effects.
Interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
s can also be used effectively together with retinoid
Retinoid
The 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.
Cimetidine
Cimetidine
Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
was reported to be effective because of its depressing mitogen
Mitogen
A mitogen is a chemical substance that encourages a cell to commence cell division, triggering mitosis. A mitogen is usually some form of a protein.Mitogenesis is the induction of mitosis, typically via a mitogen....
-induced lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
proliferation and Regulatory T cell
Regulatory T cell
Regulatory T cells , sometimes known as suppressor T cells, are a specialized subpopulation of T cells which suppresses activation of the immune system and thereby maintains tolerance to self-antigens. The existence of regulatory T cells was the subject of significant controversy among...
activity features. A report by Oliveira et al. showed that cimetidine was ineffective. Hayashi et al. applied topical calcipotriol
Calcipotriol
Calcipotriol 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. A patient of dermatologist Carmen Madeleine Curea, his pictures appeared on numerous blogs and Romanian press sources. Curea works with Spitalul Clinic Colentina in BucharestBucharest
Bucharest is the capital municipality, cultural, 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 Dâmbovița River....
, Romania
Romania
Romania is a country located at the crossroads of Central and Southeastern Europe, on the Lower Danube, within and outside the Carpathian arch, bordering on the Black Sea...
. Stephen Stone, past president of the American Academy of Dermatology
American Academy of Dermatology
The American Academy of Dermatology is the largest organization of dermatologists in the world. It was founded in 1938 and represents 17,000 dermatologists in the United States, Canada, and around the world. The Academy grants Fellowships and Associate Memberships, as well as Fellowships for...
, 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 Channel
Discovery Channel
Discovery Channel is an American satellite and cable specialty channel , founded by John Hendricks and distributed by Discovery Communications. It is a publicly traded company run by CEO David Zaslav...
and TLC
TLC (TV channel)
TLC is an American cable TV specialty channel which initially focused on educational content. 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 networks...
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 26 August 2008, Dede returned home following surgery to remove 6 kg (13 lb) of warts from his body. The surgery consisted of three steps:
- Removal of the thick carpet of warts and massive horns on his hand.
- 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. The Discovery Channel funded a blood analysis and found he lacked an immune system antigen to fight yeast infection. He was offered to have more tests run to determine whether it is treatable, and the doctor was fairly optimistic, but he refused the treatment.
In 2009 the Discovery Channel episode "Treeman Meets Treeman" reported on another Indonesian man, from the same region as Dede, who also has the disease and was given a similar treatment for it. Thus far his treatment seems to have worked better.
According to The Jakarta Post, Dede underwent the first of a series of new surgical procedures to remove the regrown warts in the spring of 2011. Surgery has however proven to be a temporary solution for Dede as the warts continue to reemerge. He has thus undergone three surgical operations since his major surgery in 2008, which was covered by the Discovery channel. At the end of December 2010, two doctors from Japan, affiliated with the Japanese Society for Complementary and Alternative Medicine came and brought Dede alternative medicine in powder form, made from coix seeds. The medicine is still undergoing a lab test.
Television
A character with epidermodysplasia verruciformis was profiled on season 5, episode 20 of Nip/TuckNip/Tuck
Nip/Tuck is an American drama series created by Ryan Murphy, which aired on FX in the United States. The series focuses on McNamara/Troy, a plastic surgery practice, and follows its founders, Sean McNamara and Christian Troy...
in 2009.
Additionally, a similar case was featured on Grey's Anatomy season 7
Grey's Anatomy (season 7)
Season seven of Grey's Anatomy, an American medical drama television series developed by Shonda Rhimes, began airing on September 23, 2010 on ABC. The season concluded on May 19, 2011.-Main cast:*Ellen Pompeo as Meredith Grey...
in 2010.
External links
- The Doctor's Doctor
- Atlas of Genetics and Cytogenetics in Oncology and Haematology
- IDR factfile
- DermIS
- At Home With the 'Tree Man' of Java slideshow by Life magazine
- Tree man who grew roots hopes to marry after 4lb of warts removed (the Daily TelegraphThe Daily TelegraphThe Daily Telegraph is a daily morning broadsheet newspaper distributed throughout the United Kingdom and internationally. The newspaper was founded by Arthur B...
Report)