Epidermodysplasia verruciformis

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Epidermodysplasia verruciformis
Other namesLewandowsky–Lutz dysplasia
Specialty Dermatology
Causes Genetic
TreatmentSurgery

Epidermodysplasia verruciformis (EV) [1] is a skin condition characterised by warty skin lesions. [2] It results from an abnormal susceptibility to HPV infection (HPV). It is associated with a high lifetime risk of squamous cell carcinomas in skin. [2] It generally presents with scaly spots and small bumps particularly on the hands, feet, face, and neck; typically beginning in childhood or a young adult. [2] The bumps tend to be flat, grow in number, and then merge to form plaques. [2] On the trunk, it typically appears like pityriasis versicolor; lesions are slightly scaly and tan, brown, red, or pale. [2] On the elbows, it may appear like psoriasis. [2] On the forehead, neck, and trunk, the lesions may appear like seborrheic keratosis. [2]

Contents

It is most frequently inherited as an autosomal recessive trait, with some reports of autosomal dominant and X-linked inheritance. [2] [3] 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. [3] [4] It is characterized by an inability to protect against HPV infection of skin. [5] [6] HPV types 5 and 8 are detected in around 90% of skin cancers in people with EV. [2] Other types are also associated with EV. [2] In rare cases, warts may develop into giant horns resulting in treeman syndrome. [7]

Prevention of skin cancer requires sun protection. [2] Treatment typically involves surgery; sometimes with the addition of skin grafting. [2] Medications used to treat the lesions include ALA-PDT (photodynamic therapy with aminolevulinic acid), applying 5-FU, imiquimod, and retinoids by mouth. [2] The lesions tend to recur on stopping treatment. [2]

The condition is rare. [2] The lesions have been noted to occur at a younger age in warmer climates. [2] EV associated skin cancer develops less frequently in Africans. [2] The condition was first described by Felix Lewandowsky and Wilhelm Lutz in 1922. [8]

Signs and symptoms

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. [9]

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. Some cases have only a few lesions which are limited to one extremity. [10] [11]

Genetics

Most patients with classic EV carry biallelic 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). [12] The EVER1 or EVER2 genes are located adjacent to one another on chromosome 17. [13] 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. [14]

Other genes have also rarely been associated with this condition. These include the ras homolog gene family member H. [15]

Diagnosis

Treatment

No curative treatment against EV has been found yet. Several treatments have been suggested, and acitretin 0.5–1 mg/day for 6 months 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 precedence to prevent the development of cutaneous tumors.[ citation needed ]

Notable cases

Ion Toader

In March 2007, a Romanian man named Ion Toader was diagnosed with this condition. [16] 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

In November 2007, a video of a 35-year-old Indonesian man named Dede Koswara with a similar disease appeared on the Internet. [17] 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". [18] On August 12, 2008, Koswara's story was the subject of an ABC's Medical Mystery episode entitled "Tree Man". [19]

On 26 August 2008, Koswara returned home following surgery to remove 6 kg (13 lb) of warts from his body. [20] The surgery consisted of three steps:

In all, 96% of the warts were removed. [20] 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 to manage the warts. [21] 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 was 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. [22]

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 received a similar treatment. His treatment seemed to have worked better.[ citation needed ]

Sahana Khatun

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. [23]

Mohammed Taluli

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. [24]

Cristhél Suyapa Martínez

In October 2018, a five-year-old girl in Honduras, Cristhél Suyapa Martínez, was diagnosed with the condition. [25]

Sebastian Quinn

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. [26]

References

  1. ↑ Logan CM, Rice MK (1987). Logan's Medical and Scientific Abbreviations (Hardbound book). J. B. Lippincott. p. 183. ISBN   0-397-54589-4.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 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.
  3. 1 2 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.
  4. ↑ 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.
  5. ↑ Myers, David J.; Kwan, Eddie; Fillman, Eric P. (2022). "Epidermodysplasia Verruciformis". StatPearls. StatPearls Publishing. PMID   30480937.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ Cardoso, JC; Calonje, E (September 2011). "Cutaneous manifestations of human papillomaviruses: a review" (PDF). Acta Dermatovenerologica Alpina, Pannonica, et Adriatica. 20 (3): 145–54. doi:10.15570/archive/acta-apa-11-3/6 (inactive 17 July 2025). PMID   22131115.{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link)
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ Allen, Mark (12 March 2007). "Missionary encounters extremely bizarre skin condition in Eastern Europe". Beware of the Blog. WFMU . Retrieved 6 August 2009.
  17. ↑ "The man who looks like a tree". Metro . 22 November 2007. Archived from the original on 24 September 2008. Retrieved 6 August 2009.
  18. ↑ "Half Man Half Tree". Discovery Channel. Archived from the original on 1 September 2008. Retrieved 6 August 2009.
  19. ↑ ""Tree Man" Medical Mystery". ABC News. 15 August 2008. Retrieved 19 December 2012.
  20. 1 2 "Indonesia's 'tree man' comes home after treatment". Los Angeles Times . Reuters. 28 August 2008. Retrieved 6 August 2009.
  21. ↑ 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.
  22. ↑ Sabtu (30 January 2016). "Dede Koswara Embuskan Nafas Terakhir, Ini Penyebab Kematian 'Manusia Akar' Bandung". Tribun Regional. Retrieved 1 February 2016.
  23. ↑ "Bangladeshi girl may be first female with 'tree man syndrome'". BBC News. 2017-01-31. Retrieved 2017-02-02.
  24. ↑ "Israeli doctors successfully operate on Gaza 'tree man'". Times of Israel. 2017-08-30. Retrieved 2017-08-30.
  25. ↑ "Extraño caso de "niña árbol" en Honduras". La Tribuna. October 23, 2018.
  26. ↑ "Man Suffering From Rare Skin Disease Epidermodysplasia Verruciformis Gets Life-Changing Surgery". Inside Edition. 2021-01-24. Retrieved 2021-02-01.

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