Epidermodysplasia verruciformis

Epidermodysplasia verruciformis
Classification and external resources
OMIM	226400 305350
DiseasesDB	31394
eMedicine	derm/123
MeSH	D004819

Epidermodysplasia verruciformis (also called Lewandowsky-Lutz dysplasia or Lutz-Lewandowsky epidermodysplasia verruciformis) is an extremely rare autosomal recessive genetic^[1] hereditary skin disorder associated with a high risk of carcinoma of the skin. It is characterized by abnormal susceptibility to human papillomaviruses (HPVs) of the skin.^[2] The resulting uncontrolled HPV infections result in the growth of scaly macules and papules, particularly on the hands and feet. It is typically associated with HPV types 5 and 8,^[3] which are found in about 80% of the normal population as asymptomatic infections,^[4] although other types may also contribute.^[3]

The condition usually has an onset of between the ages of 1–20,^[5] but can occasionally present in middle-age.^[5] It is named after the physicians who first documented it, Felix Lewandowsky and Wilhelm Lutz.^[6]

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.^[1] 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.^[7]

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 tumors.

Generally cutaneous lesions are disseminated over the body, but there are some cases with only a few lesions which are limited to one extremity.^[8][9]

Treatment

A totally effective treatment method against EV has not yet been found. Several treatments have been suggested, and acitretin 0.5–1 mg/day for 6 months’ duration is the most effective treatment owing to antiproliferative and differentiation-inducing effects.

Interferons can also be used effectively together with retinoids.

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.

Notable cases

In March 2007, a Romanian man named Ion Toader was diagnosed with this condition.^[10] A patient of dermatologist Carmen Madeleine Curea, his pictures appeared on numerous blogs and Romanian press sources. Curea works with Spitalul Clinic Colentina in Bucharest, Romania. Stephen Stone, past president of the American Academy of Dermatology, confirms this is Lewandowsky-Lutz.^{[citation needed]}

In November 2007, a new video of a 34-year-old Indonesian man named Dede Koswara with a similar disease appeared on the internet.^[11] 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".^[12] And then on August 12, 2008, Dede Koswara's story was the subject of an ABC's Medical Mystery episode entitled "Tree Man".^{[citation needed]}

On 26 August 2008, Dede returned home following surgery to remove 6 kg (13 lb) of warts from his body.^[13] 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.^[13] The surgery was documented by the Discovery Channel and TLC in the episode "Treeman: Search for the Cure."^{[citation needed]} 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.^[14] 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.^[15]

Television

A character with epidermodysplasia verruciformis was profiled on season 5, episode 20 of Nip/Tuck in 2009.

Additionally, a similar case was featured on Grey's Anatomy season 7 in 2010.^[16]

See also

• List of cutaneous conditions

References

1. ^ ^{a b} Ramoz N, Rueda LA, Bouadjar B, Montoya LS, Orth G, Favre M (December 2002). "Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis". Nature Genetics 32 (4): 579–81. doi:10.1038/ng1044. PMID 12426567. 
2. ^ Lazarczyk M, Pons C, Mendoza JA, Cassonnet P, Jacob Y, Favre M (January 2008). "Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses". The Journal of Experimental Medicine 205 (1): 35–42. doi:10.1084/jem.20071311. PMC 2234378. PMID 18158319. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2234378. 
3. ^ ^{a b} Orth G (1986). "Epidermodysplasia verruciformis: a model for understanding the oncogenicity of human papillomaviruses". Ciba Foundation Symposium 120: 157–74. PMID 3013521. 
4. ^ Antonsson A, Forslund O, Ekberg H, Sterner G, Hansson BG (December 2000). "The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses". Journal of Virology 74 (24): 11636–41. doi:10.1128/JVI.74.24.11636-11641.2000. PMC 112445. PMID 11090162. http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=11090162. 
5. ^ ^{a b} Gül U, Kiliç A, Gönül M, Cakmak SK, Bayis SS (October 2007). "Clinical aspects of epidermodysplasia verruciformis and review of the literature". International Journal of Dermatology 46 (10): 1069–72. doi:10.1111/j.1365-4632.2006.03014.x. PMID 17910717. 
6. ^ Lewandowsky-Lutz dysplasia: Who Named It?
7. ^ Lazarczyk M, Favre M (December 2008). "Role of Zn2+ ions in host-virus interactions". Journal of Virology 82 (23): 11486–94. doi:10.1128/JVI.01314-08. PMC 2583646. PMID 18787005. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2583646. 
8. ^ Lowy DR, Androphy EJ (2003). "Warts". In Freedberg IM, Eisen AZ, Wolff K, et al. Fitzpatrick's Dermatology in General Medicine (6th ed.). New York City: McGraw-Hill. pp. 2119–2131. ISBN 978-0-07-138076-8. 
9. ^ Pereira de Oliveira WR, Carrasco S, Neto CF, Rady P, Tyring SK (March 2003). "Nonspecific cell-mediated immunity in patients with epidermodysplasia verruciformis". The Journal of Dermatology 30 (3): 203–9. PMID 12692356. http://www.dermatol.or.jp/Journal/JD/2003/030030203.html. 
10. ^ Allen, Mark (12 March 2007). "Missionary encounters extremely bizarre skin condition in Eastern Europe". Beware of the Blog. WFMU. http://blog.wfmu.org/freeform/2007/03/missionary_enco.html. Retrieved 6 August 2009. 
11. ^ "The man who looks like a tree". Metro. 22 November 2007. http://www.metro.co.uk/weird/article.html?in_article_id=76668. Retrieved 6 August 2009. 
12. ^ "Half Man Half Tree". Discovery Channel. http://www.discoverychannel.co.uk/myshockingstory/halfman/index.shtml. Retrieved 6 August 2009. 
13. ^ ^{a b} Reuters (28 August 2008). "Indonesia's 'tree man' comes home after treatment". Los Angeles Times (Los Angeles Times). http://www.latimes.com/business/la-on-treeman28-2008aug28,0,3563028.story. Retrieved 6 August 2009. 
14. ^ Nathalia, Telly; Reuters (20 December 2008). "'Tree man's' warts growing again". The Australian. http://www.theaustralian.news.com.au/story/0,25197,24826865-12335,00.html. Retrieved 6 August 2009. 
15. ^ http://www.thejakartapost.com/news/2011/01/13/%E2%80%98tree-man%E2%80%99-undergoes-2hour-surgery-remove-warts.html
16. ^ Marinis, Meg (2010-10-07). "Superfreak". American Broadcasting Company/ABC.com. http://abc.go.com/shows/greys-anatomy/medical-case-file/ThemeGallery/579093. Retrieved 2010-12-21. 

Further reading

• Yabe Y, Sadakane H (September 1975). "The virus of epidermodysplasia verruciformis: electron microscopic and fluorescent antibody studies". The Journal of Investigative Dermatology 65 (3): 324–30. doi:10.1111/1523-1747.ep12598388. PMID 808576. 
• Lewandowsky F, Lutz W (October 1922). "Ein Fall einer bisher nicht beschriebenen Hauterkrankung (Epidermodysplasia verruciformis)" (in German). Archiv für Dermatologie und Syphilis 141 (2): 193–203. doi:10.1007/BF01938833. 

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 Telegraph Report)