Main Article Content


Epidermodysplasia Verruciformis (EV), often known as tree man disease, is a frightening, rare, and genetically transmitted skin ailment caused by the human papillomavirus (HPV). It is characterised by the development of a variety of flat, wart-like lesions and confluent plaques on the skin, as well as an increased risk of developing skin cancer. Cancer is primarily caused by the HPV-5 and HPV-8 viruses. Susceptibility to HPV was recently linked to a 1cm area on chromosome 17q25 by a biallelic loss-of-function mutation in either the EVER1/TMC6 or EVER2/TMC8 genes. Histological analysis of the afflicted tissue reveals acanthosis and hyperkeratosis. Amplification of the polymerase chain reaction (PCR) can be performed to detect the virus in lesions. Although there is no cure for EV, symptoms can be reduced with vitamins, antiviral medications, cryotherapy, and surgical excision of lesions.



Skin cancer DNA

Article Details

How to Cite
Gaddam Raghu Goud, Anantha Lakshmi Jakka, Patha Rasagna, & Mantripragada Bhagavan Raju. (2022). An Overview of Epidermodysplasia Verruciformis. International Journal of Research in Pharmacology & Pharmacotherapeutics, 11(2), 76-84. Retrieved from


  1. 1. Emsen IM, Kabalar ME. Epidermodysplasia verruciformis: an early and unusual presentation. Can J Plast Surg. 2010;18(1):21-4. doi: 10.1177/229255031001800105, PMID 21358870.
  2. 2. Lewandowsky F, LW. A case of a previously undescribed skin disease (epidermodysplasia verruciformis) [in German]. Arch Derm Syphilol;141:193-203.
  3. 3. Lazarczyk M, Pons C, Mendoza JA, Cassonnet P, Jacob Y, Favre M. Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses. J Exp Med. 2008;205(1):35-42. 4. doi: 10.1084/jem.20071311, PMID 18158319.
  4. 4. Jablonska S, Milewski B, Kenntnis Z. Epidermodysplasia verruciformis Lewandowsky-Lutz. Dermatologica. 1957;115:1-22.
  5. 5. Rajagopalan K, Bahru J, Loo DS, Tay CH, Chin KN, Tan KK. Familial epidermodysplasia verruciformis of Lewandowsky and Lutz. Arch Dermatol. 1972;105(1):73-8, PMID 5009624.
  6. 6. Gliński W, Jablonska S, Langner A, Obalek S, Haftek M, Proniewska M. Cell-mediated immunity in epidermodysplasia verruciformis. Dermatologica. 1976;153(4):218-27. doi: 10.1159/000251060, PMID 1017532.
  7. 7. Jablonska S, Dabrowski J, Jakubowicz K. Epidermodysplasia verruciformis as a model in studies on the role of papovaviruses in oncogenesis. Cancer Res. 1972;32(3):583-9. PMID 5061309.
  8. 8. Hammar H, Hammar L, Lambert L, Ringborg U. A case report including EM and DNA repair investigations in a dermatosis associated with multiple skin cancers: epidermodysplasia verruciformis. Acta Med Scand. 1976;200(6):441-6. doi: 10.1111/j.0954-6820.1976.tb08261.x, PMID 1015352.
  9. 9. Maddiboyina, Desu, Mallikarjun Vasam, Veerendra Teja Challa, Amareswarapu V Surendra, Sridhar Rao, Shanmugarathinam Alagarsamy, Jhawat. An insight of nanogels as novel drug delivery system with potential hybrid nanogel applications. J Biomater Sci Polym Ed. 2022;33(2):262-78. doi: 10.1080/09205063.2021.1982643, PMID 34547214.
  10. 10. Pfister H. Human papillomaviruses and skin cancer. Semin Cancer Biol. 1992;3(5):263-71. PMID 1335790.
  11. 11. Ramoz N, Taïeb A, Rueda LA, Montoya LS, Bouadjar B, Favre M, Orth G. Evidence for a nonallelic heterogeneity of epidermodysplasia verruciformis with two susceptibility loci mapped to chromosome regions 2p21-p24 and 17q25. J Invest Dermatol. 2000;114(6):1148-53. doi: 10.1046/j.1523-1747.2000.00996.x, PMID 10844558.
  12. 12. Orth G. Epidermodysplasia verruciformis. In: Howley PM, Salzman NP, editors. The papillomaviruses. New York: Plenum Press; 1987. p. 199-243.
  13. 13. Maddiboyina B, Jhawat V, Desu PK, Gandhi S, Nakkala RK, Singh S. Formulation and evaluation of thermosensitive flurbiprofen in situ Nano gel for the ocular delivery. J Biomater Sci Polym Ed. 2021;32(12):1584-97. doi: 10.1080/09205063.2021.1927460, PMID 33977874.
  14. 14. Jablonska S, Orth G. Epidermodysplasia verruciformis. Clin Dermatol. 1985;3(4):83-96. doi: 10.1016/0738-081x(85)90052-5, PMID 2850863.
  15. 15. Zahir A, Craig L, Rady P, Tyring S, Ehrlich A. Epidermodysplasia verruciformis associated with HPV 10. Dermatol Online J. 2013;19(4):2. doi: 10.5070/D379B2760C, PMID 24021362.
  16. 16. Orth G. Epidermodysplasia verruciformis. In: Salzman NP, Howley PM, editors, The Papovaviridae. The papillomaviruses. New York: Plenum Press; 1987. p. 199-243.
  17. 17. Pfister H. Human papillomaviruses and skin cancer. Semin Cancer Biol. 1992;3(5):263-71. PMID 1335790.
  18. 18. Lewandowsky F, Lutz W. ein Fall einer bisher nicht beschriebenen Hauterkrankung (Epidermodysplasia verruciformis) [Epidermodysplasia verruciformis]. Arch f Dermat. 1922;141(2):193-203. doi: 10.1007/BF01938833.
  19. 19. Mashkilleison J. N: Ist die epidermodysplasia verruciformis (Lewandowsky-Lutz)ein stelbastandige Dermatos. IHRE beziehungen zur Verrucositas, Dermat, Wchnschr. 1931;92:569.
  20. 20. Sullivan M, Ellis F. A: epidermodysplasia verruciformis (Lewandowsky and Lutz). Arch Dermatol Syph. 1939;40 (Sep):422.
  21. 21. sayer A, Schweig J. Epidermodysplasia verruciformis (Lewandowsky – Lutz)report of a case with all the essential; Aug 1942.
  22. 22. abdullah A, EPA. United States today. Network of European World Shops 10-years-old girl may be 1st female with extremely rare’ tree man syndrome’.
  23. 23. Warts starts to regrow on Bangladesh tree man after 24 surgeries.update on February 2, 2018.
  24. 24. Imahorn E, Yüksel Z, spoerri I, Gürel G, Imhof C, Saraçoğlu ZN, Koku Aksu AE, Rady PL, Tyring SK, Kempf W, Itin PH, Burger B. Novel TMC8 splice site mutations in epidermodysplasia verruciformis and review of HPV infections in patients with the disease. J Eur Acad Dermatol Venereol. 2017;31(10):1722-6. doi: 10.1111/jdv.14431, PMID 28646613.
  25. 25. Pfister H. Human papillomaviruses and skin cancer. Semin Cancer Biol. 1992;3(5):263-71. PMID 1335790.
  26. 26. Rowson KEK, Mahy BWJ. Human papova (wart) virus. Bacteriol Rev. 1967;31(2):110-31. doi: 10.1128/br.31.2.110-131.1967, PMID 5342713.
  27. 27. Epidermodysplasia verruciformis: A dreadful disease.
  28. 28. Ramoz N, Rueda LA, Bouadjar B, Montoya LS, Orth G, Favre M. Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis. Nat Genet. 2002;32(4):579-81. doi: 10.1038/ng1044, PMID 12426567.
  29. 29. Orth G. Genetics of epidermodysplasia verruciformis: insights into host defense against papillomaviruses. Semin Immunol. 2006;18(6):362-74. doi: 10.1016/j.smim.2006.07.008, PMID 17011789.
  30. 30. Azzimonti B, Mondini M, De Andrea M, Gioia D, Dianzani U, Mesturini R, Leigheb G, Tiberio R, Landolfo S, Gariglio M. CD8+ T-cell lymphocytopenia and lack of EVER mutations in a patient with clinically and virologically typical epidermodysplasia verruciformis. Arch Dermatol. 2005;141(10):1323-5. doi: 10.1001/archderm.141.10.1323, PMID 16230580.
  31. 31. Notarangelo L, Casanova JL, Fischer A, Puck J, Rosen F, Seger R, Geha R, International Union of Immunological Societies Primary Immunodeficiency diseases classification committee. Primary immunodeficiency diseases: an update. J Allergy Clin Immunol. 2004;114(3):677-87. doi: 10.1016/j.jaci.2004.06.044, PMID 15356576.
  32. 32. Lowy DR, Androphy EJ. Warts. In: Freedberg IM, Eisen AZ, Wolff K, et al, editors. Fitzpatrick’s dermatology in general medicine. 6th ed. McGraw-Hill. New York City 2003 pp. p. 2119-31.
  33. 33. Pereira de Oliveira WR, Carrasco S, Neto CF, Rady P, Tyring SK. Nonspecific cellmediated immunity in patients with epidermodysplasia verruciformis HPV. J Dermatol. 2003;30(3):203-9. doi: 10.1111/j.1346-8138.2003.tb00372.x, PMID 12692356.
  34. 34. Favre M, Orth G, Croissant O, Yaniv M. Human papillomavirus DNA: physical map. Proc Natl Acad Sci U S A. 1975;72(12):4810-4. doi: 10.1073/pnas.72.12.4810, PMID 174077.
  35. 35. Favre M, Breitburd F, Croissant O, Orth G. Chromatin-like structures obtained after alkaline disruption of bovine and human papillomaviruses. J Virol. 1977;21(3):1205-9. doi: 10.1128/JVI.21.3.1205-1209.1977, PMID 191643.
  36. 36. Orth G, Breitburd F, Favre M' & Croissant, 0. Cold Spring Harbor conferences on CellProliferation. In: Vol. 4B. Cold Spring Harbor, NY: Cold Spring Harbor Laboratories; 1977. p. 1043-68.
  37. 37. Orth G, Favre M, Croissant. J Virol. 1977;24. PMID 108120.
  38. 38. Gober MD, Rady PL, He Q, Tucker SB, Tyring SK, Gaspari AA. Novel homozygous frameshift mutation of EVER1 gene in an epidermodysplasia verruciformis patient. J Invest Dermatol. 2007; Apr;127(4):817-20. doi: 10.1038/sj.jid.5700641, PMID 17139267.
  39. 39. Sun XK, Chen JF, Xu AE. A homozygous nonsense mutation in the EVER2 gene leads to epidermodysplasia verruciformis. Clin Exp Dermatol. 2005; Sep 30;30(5):573-4. doi: 10.1111/j.1365-2230.2005.01858.x, PMID 16045695.
  40. 40. Ramoz N, Rueda LA, Bouadjar B, Montoya LS, Orth G, Favre M. Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis. Nat Genet. 2002;32(4):579-81. doi: 10.1038/ng1044, PMID 12426567.
  41. 41. Burger B, Itin PH. Epidermodysplasia verruciformis. Curr Probl Dermatol. 2014;45:123-31. doi: 10.1159/000356068, PMID 24643182.
  42. 42. Nature Publishing Group. Available from:,mutations. In: two adjacent novel genes are associated with epidermodysplasia verruciformis.
  43. 43. Androphy EJ, Dvoretzky I, Lowy DR. Xlinked inheritance of epidermodysplasia verruciformis. Genetic and virologic studies of a kindred. Arch Dermatol. 1985 Jul;121(7):864-8, PMID 2990354.
  44. 44. Li SL, Duo LN, Wang HJ, Dai W, Zhou EH, Xu YN, et al. Identification of the LCK mutation in an atypical epidermodysplasia verruciformis family with T cell defects and virus-induced squamous cell carcinoma. Br J Dermatol. 2016; Apr 18.
  45. 45. Assoc prof Emanuel P. dermatopathologist,New Zealand, 2013. Epidermodysplasia verruciformis pathology.
  46. 46. Nat Pernick MD, skin nontumer/clinical dermatology infectious disorders epidermodysplasia verruciformis.
  47. 47. Medically reviewed by Xixi Luo, M.D. on May 24, 2017-written by Jamas Roland, epidermodysplasia verruciformis: what is it and how is it treated?
  48. 48. Expert reviewer: Pr Giovanna Zambruno,Lutz-Lewandowsky epidermodysplasia verruciformis.
  49. 49. Ngan V, staff writer,2006.updated by doctor Jannet Gomez,dec,2016. Epidermodysplasia verruciformis.
  50. 50. Anadolu R, Oskay T, Erdem C, Boyvat A, Terzi E, Gürgey E. Treatment of epidermodysplasia verruciformis with a combination of acitretin and interferon alfa2a. J Am Acad Dermatol. 2001;45(2):296-9. doi: 10.1067/mjd.2001.114575, PMID 11464195.
  51. 51. Iraji F, Faghihi G. Epidermodysplasia verruciformis: association with isolated IgM deficiency and response to treatment with acitretin. Clin Exp Dermatol. 2000;25(1):41-3. doi: 10.1046/j.1365-2230.2000.00570.x, PMID 10671971.
  52. 52. Maddiboyina B, Nakkala RK. Formulation development and characterization of enteric coated tablets of lansoprazole. Pharm Lett. 2020;12:22-38.
  53. 53. Hayashi J, Matsui C, Mitsuishi T, Kawashima M, Morohashi M. Treatment of localized epidermodysplasia verruciformis with tacalcitol ointment. Int J Dermatol. 2002;41(11):817-20. doi: 10.1046/j.1365-4362.2002.01642.x, PMID 12453013.
  54. 54. Micali G, Nasca MR, Dall’Oglio F, Musumeci ML. Cimetidine therapy for epidermodysplasia verruciformis. J Am Acad Dermatol. 2003;48(2);Suppl:S9-S10. doi: 10.1067/mjd.2003.111, PMID 12582373.
  55. 55. de Oliveira WR, Neto CF, Rivitti EA. The lack of a clinical effect of cimetidine in the treatment of epidermodysplasia verruciformis. J Am Acad Dermatol. 2004;50(6):e14; author reply e15. doi: 10.1016/j.jaad.2003.12.037, PMID 15153919.
  56. 56. Berthelot C, Dickerson MC, Rady P, He Q, Niroomand F, Tyring SK, Pandya AG. Treatment of a patient with epidermodysplasia verruciformis carrying a novel EVER2 mutation with imiquimod. J Am Acad Dermatol. 2007;56(5):882-6. doi: 10.1016/j.jaad.2007.01.036, PMID 17368633.
  57. 57. Maddina BY, Asthana GS, Asthana A. Formulation and Development of polysaccharide based mesalamine Nanoparticles. Int J Pharm Clin Res. 2016;8(7):676-84.
  58. 58. Karrer S, Szeimies RM, Abels C, Wlotzke U, Stolz W, Landthaler M. Epidermodysplasia verruciformis treated using topical 5aminolaevulinic acid photodynamic therapy. Br J Dermatol. 1999;140(5):935-8. doi: 10.1046/j.1365-2133.1999.02830.x, PMID 10354037.
  59. 59. Preiser W, Kapur N, Snoeck R, Groves RW, Brink NS. No apparent effect of cidofovir in epidermodysplasia verruciformis. J Clin Virol. 2000;16(1):55-7. doi: 10.1016/s1386-6532(99)00069-4, PMID 10680741.
  60. 60. Hu W, Nuovo G, Willen M, Somach S. Epidermodysplasia verruciformis in two half-brothers with HIV infection. J Cutan Med Surg. 2004;8(5):357-60. doi: 10.1007/s10227-005-0022-6, PMID 15868315.
  61. 61. Davison SC, Francis N, McLean K, Bunker CB. Epidermodysplasia verruciformislike eruption associated with HIV infection. Clin Exp Dermatol. 2004;29(3):311-2. doi: 10.1111/j.1365-2230.2004.01503.x, PMID 15115519.
  62. 62. Maddiboyina B, Asthana A, Asthana GS, Singh S, Sunnapu O, Kotla N. Formulation and characterization of polycarbophil coated mucoadhesive microspheres of repaglinide. J Pharm Sci Res. 2015;7(11):972-7.
  63. 63. Haas N, Fuchs PG, Hermes B, Henz BM. Remission of epidermodysplasia verruciformis like skin eruption after highly active antiretroviral therapy in a human immunodeficiency virus positive patient. Br J Dermatol. 2001;145(4):669-70. doi: 10.1046/j.1365-2133.2001.04426.x, PMID 11703302.
  64. 64. Maddiboyina B, Jhawat V, Sivaraman G, Sunnapu O, Nakkala RK, Naik MH, Gulia M. Formulation Development & Characterization of controlled release core in cup matrix tablets of venlafaxine HCl. Curr Drug Ther. 2020;15(5):503-11. doi: 10.2174/1574885515666200331104440.
  65. 65. Maddiboyina B, Jhawat V, Ramesh K, Nakkala RK, Jakka AL. A review on nanoparticle-based herbal remedies for the management of alopecia. Pharm Lett. 2020;12(5):1-17.