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Epidermodysplasia verruciformis

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"Treeman" redirects here. For the fictional characters "The Treeman Twins", see Kingsman: The Red Diamond § Characters.
Epidermodysplasia verruciformis
Other namesLewandowsky–Lutz dysplasia, treeman syndrome
Abul Bajandar from Bangladesh
SpecialtyDermatology
CausesGenetic
TreatmentSurgery

Epidermodysplasia verruciformis (EV) is a skin condition characterised by warty skin lesions.[1] It results from an abnormal susceptibility to HPV infection (HPV) and is associated with a high lifetime risk of squamous cell carcinomas in skin.[1] It generally presents with scaly spots and small bumps particularly on the hands, feet, face and neck; typically beginning in childhood or in a young adult.[1] The bumps tend to be flat, grow in number and then merge to form plaques.[1] On the trunk, it typically appears like pityriasis versicolor; lesions there being slightly scaly and tan, brown, red or looking pale.[1] On the elbows, it may appear like psoriasis.[1] On the forehead, neck and trunk, the lesions may appear like seborrheic keratosis.[1]

It is most frequently inherited as an autosomal recessive trait, with some reports of autosomal dominant and X-linked inheritance.[1][2] Other types include atypical EV which develops due to gene mutations that cause an impaired immune system, and acquired EV which occurs due to acquired immunodeficiency.[2][3] It is characterized by an inability to protect against HPV infection of skin.[4][5] HPV types 5 and 8 are detected in around 90% of skin cancers in people with EV.[1] Other types are also associated with EV.[1] In rare cases, the warts may develop into giant horns resulting in treeman syndrome.[6]

Prevention of skin cancer requires sun protection.[1] Treatment typically involves surgery; sometimes with the addition of skin grafting.[1] Medications used to treat the lesions include ALA-PDT (photodynamic therapy with aminolevulinic acid), applying 5-FU, imiquimod, and retinoids by mouth.[1] The lesions tend to recur on stopping treatment.[1]

The condition is rare.[1] The lesions have been noted to occur at a younger age in warmer climates.[1] EV associated skin cancer develops less frequently in Africans.[1] The condition was first described by Felix Lewandowsky and Wilhelm Lutz in 1922.[7]

Signs and symptoms

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Clinical diagnostic features are lifelong eruptions of pityriasis versicolor-like macules, flat wart-like papules, one to many cutaneous horn-like lesions, and development of cutaneous carcinomas.[citation needed]

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 initial 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.[citation needed]

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

Genetics

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Most patients with classic EV carry bialletic loss-of-function mutations of transmembrane channel-like protein 6 (TMC6; also called EV protein 1, EVER1), TMC8 (also called EVER2), or calcium- and integrin-binding protein 1 (CIB1).[10] The EVER1 or EVER2 genes are located adjacent to one another on chromosome 17.[11] These genes play a role in regulating the distribution of zinc in the cell nuclei. Zinc is a necessary cofactor for many viral proteins, and the activity of EVER1/EVER2 complex appears to restrict the access of viral proteins to cellular zinc stores, limiting their growth.[12]

Other genes have also rarely been associated with this condition. These include the ras homolog gene family member H.[13]

Diagnosis

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Treatment

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No curative treatment against EV has been found yet. 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.[citation needed]

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.[citation needed]

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.[citation needed]

Notable cases

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Ion Toader

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In March 2007, a Romanian man named Ion Toader was diagnosed with this condition.[14] 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, confirmed that this was Lewandowsky–Lutz.[citation needed] Toader underwent surgery in late 2013, and since then has been mostly symptom-free, with only small reappearances.

Dede Koswara

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In November 2007, a video of a 35-year-old Indonesian man named Dede Koswara with a similar disease appeared on the Internet.[15] His story appeared on the U.S. Discovery Channel and TLC series My Shocking Story (Extraordinary People on UK's Five) in the episode "Half Man Half Tree".[16] On August 12, 2008, Koswara's story was the subject of an ABC's Medical Mystery episode entitled "Tree Man".[17]

On 26 August 2008, Koswara returned home following surgery to remove 6 kg (13 lb) of warts from his body.[18] The surgery consisted of three steps:

  • Removal of the thick carpet of warts and massive horns on his hands
  • Removal of the smaller warts on his head, torso, and feet
  • Covering of the hands with grafted skin

In all, 96% of the warts were removed.[18] The surgery was documented by the Discovery Channel and TLC in the episode "Treeman: Search for the Cure".[citation needed] However, his warts returned and he was thought to require two surgeries per year for the rest of his life in order to manage the warts.[19] 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.[citation needed]

According to The Jakarta Post, Koswara underwent the first of a series of new surgical procedures to remove the regrown warts in the spring of 2011. Surgery had, however, proven to be a temporary solution for Koswara, as the warts continued to re-emerge. He had thus undergone three surgical operations since his major surgery in 2008. At the end of December 2010, two doctors from the Japanese Society for Complementary and Alternative Medicine brought him a drug made from Job's tears. The medicine was still undergoing lab tests as of 2016.[citation needed]

Koswara died on 30 January 2016 at Hasan Sadikin Hospital, Bandung, from the complications related to his condition.[20]

In 2009, the Discovery Channel episode "Treeman Meets Treeman" reported on another Indonesian man, from the same region as Koswara, who also has the disease and was given a similar treatment for it. His treatment seemed to have worked better.[citation needed]

Abul Bajandar

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In January 2016, a 25-year-old patient named Abul Bajandar from Khulna, Bangladesh was admitted in Dhaka Medical College and Hospital and was diagnosed with this condition. Doctors at the hospital decided to form a medical board for the treatment of the patient.[21][22] Over the following year, Bajandar underwent at least 25 surgeries for the removal of the warts—weighing in excess of 5 kg (11 lb)—from his hands, feet, and legs.[23][24][25] Bajandar’s condition returned after he interrupted treatments in May 2018. His doctors requested that he return for treatment many times. He finally returned for treatment in late 2018, but his condition had significantly worsened and spread to his feet. He will reportedly need five to six operations to get the condition back under control.[26] In June 2019, he requested to get his hands amputated as the pain is unbearable.[27] As of July 2023, doctors had refused amputation as a solution and insisted on continuous minor surgeries to manage the condition, which would be provided free of charge by the Bangladeshi government.[28]

Sahana Khatun

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In January 2017, it was reported that a 10-year-old girl in Bangladesh, Sahana Khatun, was diagnosed after developing lesions four months earlier. BBC News said that the case may have been the first diagnosis in a female.[29]

Mohammed Taluli

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In August 2017, it was reported that a 42-year-old man from Gaza, Mohammed Taluli, had been successfully operated on at the Hadassah Medical Centre in Jerusalem.[30]

Cristhél Suyapa Martínez

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In October 2018, a five-year-old girl in Honduras, Cristhél Suyapa Martínez, was diagnosed with the condition.[31]

Sebastian Quinn

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Sebastian Quinn is a Pittsburgh man with the condition who featured as a patient on an episode of TLC's My Feet Are Killing Me in January 2021. His overseeing specialist Ebonie Vincent operated on him to manage the growths on his feet.[32]

References

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  1. ^ a b c d e f g h i j k l m n o p q James, William D.; Elston, Dirk; Treat, James R.; Rosenbach, Misha A.; Neuhaus, Isaac (2020). "19. Viral diseases: epidermodysplasia verruciformis". Andrews' Diseases of the Skin: Clinical Dermatology (13th ed.). Edinburgh: Elsevier. pp. 411–412. ISBN 978-0-323-54753-6.
  2. ^ a b Shimizu, Akira; Yamaguchi, Reimon; Kuriyama, Yuko (March 2023). "Recent advances in cutaneous HPV infection". The Journal of Dermatology. 50 (3): 290–298. doi:10.1111/1346-8138.16697. ISSN 1346-8138. PMID 36601717. S2CID 255476033.
  3. ^ Moore, Stephen; Rady, Peter; Tyring, Stephen (November 2022). "Acquired epidermodysplasia verruciformis: clinical presentation and treatment update". International Journal of Dermatology. 61 (11): 1325–1335. doi:10.1111/ijd.15857. ISSN 1365-4632. PMID 34403500. S2CID 237198699.
  4. ^ Myers, David J.; Kwan, Eddie; Fillman, Eric P. (2022). "Epidermodysplasia Verruciformis". StatPearls. StatPearls Publishing. PMID 30480937.
  5. ^ Mogensen, Trine H. (November 2022). "Genetic susceptibility to viral disease in humans". Clinical Microbiology and Infection. 28 (11): 1411–1416. doi:10.1016/j.cmi.2022.02.023. ISSN 1469-0691. PMID 35218976. S2CID 247114913.
  6. ^ Uitto, Jouni; Saeidian, Amir Hossein; Youssefian, Leila; Saffarian, Zahra; Casanova, Jean-Laurent; Béziat, Vivien; Jouanguy, Emmanuelle; Vahidnezhad, Hassan (May 2022). "Recalcitrant Warts, Epidermodysplasia Verruciformis, and the Tree-Man Syndrome: Phenotypic Spectrum of Cutaneous Human Papillomavirus Infections at the Intersection of Genetic Variability of Viral and Human Genomes". The Journal of Investigative Dermatology. 142 (5): 1265–1269. doi:10.1016/j.jid.2021.10.029. ISSN 1523-1747. PMC 9038624. PMID 34843682.
  7. ^ Emsen, IM; Kabalar, ME (2010). "Epidermodysplasia verruciformis: An early and unusual presentation". The Canadian Journal of Plastic Surgery. 18 (1): 21–4. doi:10.1177/229255031001800105. PMC 2851455. PMID 21358870. S2CID 207964064.
  8. ^ Lowy DR, Androphy EJ (2003). "Warts". In Freedberg IM, Eisen AZ, Wolff K, et al. (eds.). 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 HPV". The Journal of Dermatology. 30 (3): 203–9. doi:10.1111/j.1346-8138.2003.tb00372.x. PMID 12692356. S2CID 27427426. Archived from the original on 2010-02-04.
  10. ^ Casanova, Jean-Laurent (26 November 2021). "Mechanisms of viral inflammation and disease". Science. 374 (6571): 1080–1086. doi:10.1126/science.abj7965. PMC 8697421. PMID 34822298.
  11. ^ 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. S2CID 20013445.
  12. ^ 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.
  13. ^ Crequer, Amandine; Troeger, Anja; Patin, Etienne; Ma, Cindy; Picard, Capucine; Pedergnana, Vincent; Fieschi, Claire; Lim, Annick; Abhyankar, Avinash; Gineau, Laure; Mueller-Fleckenstein, Ingrid; Schmidt, Monika; Taieb, Alain; Krueger, James; Abel, Laurent; Tangye, Stuart; Orth, Gérard; Williams, David; Casanova, Jean-Laurent; Jouanguy, Emmanuelle (2012-08-01). "Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections". The Journal of Clinical Investigation. 122 (9): 3239–3247. doi:10.1172/JCI62949. PMC 3428089. PMID 22850876.
  14. ^ Allen, Mark (12 March 2007). "Missionary encounters extremely bizarre skin condition in Eastern Europe". Beware of the Blog. WFMU. Retrieved 6 August 2009.
  15. ^ "The man who looks like a tree". Metro. 22 November 2007. Archived from the original on 24 September 2008. Retrieved 6 August 2009.
  16. ^ "Half Man Half Tree". Discovery Channel. Archived from the original on 1 September 2008. Retrieved 6 August 2009.
  17. ^ ""Tree Man" Medical Mystery". ABC News. 15 August 2008. Retrieved 19 December 2012.
  18. ^ a b "Indonesia's 'tree man' comes home after treatment". Los Angeles Times. Reuters. 28 August 2008. Retrieved 6 August 2009.
  19. ^ Nathalia, Telly (20 December 2008). "'Tree man's' warts growing again". The Australian. Reuters. Archived from the original on 12 September 2009. Retrieved 6 August 2009.
  20. ^ Sabtu (30 January 2016). "Dede Koswara Embuskan Nafas Terakhir, Ini Penyebab Kematian 'Manusia Akar' Bandung". Tribun Regional. Retrieved 1 February 2016.
  21. ^ "Rare disease: DMCH to form medical board tomorrow". The Daily Star. 2016-01-30. Retrieved 2016-01-30.
  22. ^ "বিরল এই বৃক্ষ মানব রোগ হয়েছে বাংলাদেশে একজনেরই – BBC বাংলা". BBC বাংলা (in Bengali). BBC. 30 January 2016. Retrieved 2016-01-30.
  23. ^ Bangladesh's 'Tree Man' to undergo surgery, The Guardian, 31 January 2016.
  24. ^ "Now I am well, says Bangladeshi Tree Man". Retrieved 2016-07-11.
  25. ^ "Hope for Bangladesh 'Tree Man' after 16 surgeries to remove growths". Al Arabiya. AFP. 10 January 2017.
  26. ^ "'Big mistake for me to leave': Man's 'tree man' condition returns worse than before after interrupting treatments". Archived from the original on 2019-06-26. Retrieved 2019-01-23.
  27. ^ "Bangladesh 'Tree Man' wants hands amputated". Gulf News.
  28. ^ "His dream came true. But for viral 'tree man', much worse was to come". South China Morning Post. 2023-07-23. Retrieved 2024-09-28.
  29. ^ "Bangladeshi girl may be first female with 'tree man syndrome'". BBC News. 2017-01-31. Retrieved 2017-02-02.
  30. ^ "Israeli doctors successfully operate on Gaza 'tree man'". Times of Israel. 2017-08-30. Retrieved 2017-08-30.
  31. ^ "Extraño caso de "niña árbol" en Honduras". La Tribuna. October 23, 2018.
  32. ^ "Man Suffering From Rare Skin Disease Epidermodysplasia Verruciformis Gets Life-Changing Surgery". Inside Edition. 2021-01-24. Retrieved 2021-02-01.

Further reading

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