Epidermodysplasia verruciformis

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Epidermodysplasia verruciformis
Other namesLewandowsky–Lutz dysplasia, treeman syndrome
World's 4th a Tree Man.jpg
Abul Bajandar from Bangladesh
Specialty Dermatology
Causes Genetic
TreatmentSurgery

Epidermodysplasia verruciformis (EV) is a skin condition characterised by warty skin lesions. [1] It results from an abnormal susceptibility to HPV infection (HPV). It 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 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 are 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]

Contents

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, 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

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. [8]

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. [9] [10]

Genetics

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). [11] The EVER1 or EVER2 genes are located adjacent to one another on chromosome 17. [12] 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. [13]

Other genes have also rarely been associated with this condition. These include the ras homolog gene family member H. [14]

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 preference 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. [15] 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. [16] 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". [17] On August 12, 2008, Koswara's story was the subject of an ABC's Medical Mystery episode entitled "Tree Man". [18]

On 26 August 2008, Koswara returned home following surgery to remove 6 kg (13 lb) of warts from his body. [19] The surgery consisted of three steps:

In all, 96% of the warts were removed. [19] 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. [20] 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. [21]

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 ]

Abul Bajandar

In January 2016, a 25-year-old patient named Abul Bajandar from Khulna, Bangladesh was admitted to Dhaka Medical College and Hospital and was diagnosed with this condition. Doctors at the hospital decided to form a medical board to treat the patient. [22] [23] Over the following year, Bajandar underwent at least 25 surgeries for the removal of the warts—weighing more than 5 kg (11 lb)—from his hands, feet, and legs. [24] [25] [26] 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. [27] In June 2019, he requested to get his hands amputated as the pain is unbearable. [28] 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. [29]

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. [30]

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. [31]

Cristhél Suyapa Martínez

In October 2018, a five-year-old girl in Honduras, Cristhél Suyapa Martínez, was diagnosed with the condition. [32]

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. [33]

Related Research Articles

<span class="mw-page-title-main">Wart</span> Small, rough growth resembling a cauliflower or a solid blister

Warts are non-cancerous viral growths usually occurring on the hands and feet but which can also affect other locations, such as the genitals or face. One or many warts may appear. They are distinguished from cancerous tumors as they are caused by a viral infection, such as a human papillomavirus, rather than a cancer growth.

<span class="mw-page-title-main">Human papillomavirus infection</span> Human disease

Human papillomavirus infection is caused by a DNA virus from the Papillomaviridae family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, tonsils, or throat. Nearly all cervical cancer is due to HPV, and two strains – HPV16 and HPV18 – account for 70% of all cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers. Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis.

<span class="mw-page-title-main">Genital wart</span> Sexually transmitted infection caused by certain types of human papillomaviruses

Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They may be flat or project out from the surface of the skin, and their color may vary; brownish, white, pale yellow, pinkish-red, or gray. There may be a few individual warts or several, either in a cluster or merged together to look cauliflower-shaped. They can be itchy and feel burning. Usually they cause few symptoms, but can occasionally be painful. Typically they appear one to eight months following exposure. Warts are the most easily recognized symptom of genital HPV infection.

<span class="mw-page-title-main">Plantar wart</span> Medical condition

A plantar wart is a wart occurring on the bottom of the foot or toes. Its color is typically similar to that of the skin. Small black dots often occur on the surface. One or more may occur in an area. They may result in pain with pressure such that walking is difficult.

<span class="mw-page-title-main">Lichen planus</span> Human chronic inflammatory disease

Lichen planus (LP) is a chronic inflammatory and autoimmune disease that affects the skin, nails, hair, and mucous membranes. It is not an actual lichen, but is named for its appearance. It is characterized by polygonal, flat-topped, violaceous papules and plaques with overlying, reticulated, fine white scale, commonly affecting dorsal hands, flexural wrists and forearms, trunk, anterior lower legs and oral mucosa. The hue may be gray-brown in people with darker skin. Although there is a broad clinical range of LP manifestations, the skin and oral cavity remain as the major sites of involvement. The cause is unknown, but it is thought to be the result of an autoimmune process with an unknown initial trigger. There is no cure, but many different medications and procedures have been used in efforts to control the symptoms.

<span class="mw-page-title-main">Seborrheic keratosis</span> Benign skin tumor originating in keratocytes

A seborrheic keratosis is a non-cancerous (benign) skin tumour that originates from cells, namely keratinocytes, in the outer layer of the skin called the epidermis. Like liver spots, seborrheic keratoses are seen more often as people age.

<span class="mw-page-title-main">Actinic keratosis</span> Rough skin induced by UV exposure

Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin. Actinic keratosis is a disorder of epidermal keratinocytes that is induced by ultraviolet (UV) light exposure.

A skin infection is an infection of the skin in humans and other animals, that can also affect the associated soft tissues such as loose connective tissue and mucous membranes. They comprise a category of infections termed skin and skin structure infections (SSSIs), or skin and soft tissue infections (SSTIs), and acute bacterial SSSIs (ABSSSIs). They are distinguished from dermatitis, although skin infections can result in skin inflammation.

<span class="mw-page-title-main">Vulvar cancer</span> Cancer involving the vulva

Vulvar cancer is a cancer of the vulva, the outer portion of the female genitals. It most commonly affects the labia majora. Less often, the labia minora, clitoris, or Bartholin's glands are affected. Symptoms include a lump, itchiness, changes in the skin, or bleeding from the vulva.

<span class="mw-page-title-main">Cutaneous horn</span> Medical condition

Cutaneous horns, also known by the Latin name cornu cutaneum, are unusual keratinous skin tumors with the appearance of horns, or sometimes of wood or coral. Formally, this is a clinical diagnosis for a "conical projection above the surface of the skin." They are usually small and localized but can, in very rare cases, be much larger. Although often benign, they can also be malignant or premalignant.

<span class="mw-page-title-main">TMC6</span> Protein-coding gene in the species Homo sapiens

Transmembrane channel-like protein 6 is a protein that in humans is encoded by the TMC6 gene. In vivo, TMC6 and its homolog TMC8, interact and form a complex with the zinc transporter 1 (SLC30A1) and localize mostly to the endoplasmic reticulum, but also to the nuclear membrane and Golgi apparatus.

Florid cutaneous papillomatosis (FCP) is an obligate paraneoplastic syndrome.

<span class="mw-page-title-main">Periungual wart</span> Medical condition

Periungual warts are warts that cluster around the fingernail or toenail. They appear as thickened, fissured cauliflower-like skin around the nail plate. Periungual warts often cause loss of the cuticle and paronychia. Nail biting increases susceptibility to these warts.

Madarosis is a condition that results in the loss of eyelashes, and sometimes eyebrows. The term "madarosis" is derived from the ancient Greek "madaros", meaning "bald". Eyelashes are important in the prevention of bacteria and other foreign objects entering the eye. Some studies found that between 45 and 76 percent of patients with various types of leprosy had madarosis.

<span class="mw-page-title-main">TMC8</span> Protein-coding gene in the species Homo sapiens

Transmembrane channel-like protein 8 is a protein which in humans is encoded by the TMC8 gene.

<span class="mw-page-title-main">Acrokeratosis verruciformis</span> Medical condition

Acrokeratosis verruciformis is a rare autosomal dominant disorder appearing at birth or in early childhood, characterized by skin lesions that are small, verrucous, flat papules resembling warts along with palmoplantar punctate keratoses and pits. However sporadic forms, whose less than 10 cases have been reported, presents at a later age, usually after the first decade and generally lack palmoplantar keratoses. Whether acrokeratosis verruciformis and Darier disease are related or distinct entities has been controversial, like Darier's disease, it is associated with defects in the ATP2A2 gene. however the specific mutations found in the ATP2A2 gene in acrokeratosis verruciformis have never been found in Darier's disease.

<span class="mw-page-title-main">Bowenoid papulosis</span> Medical condition

Bowenoid papulosis is a cutaneous condition characterized by the presence of pigmented verrucous papules on the body of the penis. They are associated with human papillomavirus, the causative agent of genital warts.

<span class="mw-page-title-main">Trichodysplasia spinulosa</span> Medical condition

Trichodysplasia spinulosa is a rare cutaneous condition that has been described almost exclusively in immunocompromised patients, usually organ transplant recipients, on regimens of immunosuppressive drugs. As of early 2016, a total of 32 cases had been reported in the medical literature. Despite its rarity, TS is believed to be underdiagnosed, and the growing population of patients on immunosuppressive drug regimens suggests its incidence may rise. TS has been described as an emerging infectious disease.

Gérard Orth was a French virologist, emeritus research director at the CNRS, honorary professor at the Pasteur Institute.

Dede Koswara, also known as the "Tree Man", was an Indonesian carpenter with epidermodysplasia verruciformis (EV), a rare disease that causes the human papillomavirus (HPV) to grow uncontrollably, leading to the development of warts resembling tree bark. He received criticism from the people around him for having an unknown disease for most of his life. It was not until his later years that he received notoriety and was given multiple treatments for his condition.

References

  1. 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.
  2. 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.
  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. ↑ Cardoso, JC; Calonje, E (September 2011). "Cutaneous manifestations of human papillomaviruses: a review" (PDF). Acta dermatovenerologica Alpina, Pannonica, et Adriatica. 20 (3): 145–54. PMID   22131115.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ Allen, Mark (12 March 2007). "Missionary encounters extremely bizarre skin condition in Eastern Europe". Beware of the Blog. WFMU . Retrieved 6 August 2009.
  16. ↑ "The man who looks like a tree". Metro . 22 November 2007. Archived from the original on 24 September 2008. Retrieved 6 August 2009.
  17. ↑ "Half Man Half Tree". Discovery Channel. Archived from the original on 1 September 2008. Retrieved 6 August 2009.
  18. ↑ ""Tree Man" Medical Mystery". ABC News. 15 August 2008. Retrieved 19 December 2012.
  19. 1 2 "Indonesia's 'tree man' comes home after treatment". Los Angeles Times . Reuters. 28 August 2008. Retrieved 6 August 2009.
  20. ↑ 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.
  21. ↑ Sabtu (30 January 2016). "Dede Koswara Embuskan Nafas Terakhir, Ini Penyebab Kematian 'Manusia Akar' Bandung". Tribun Regional. Retrieved 1 February 2016.
  22. ↑ "Rare disease: DMCH to form medical board tomorrow". The Daily Star . 2016-01-30. Retrieved 2016-01-30.
  23. ↑ "বিরল এই বৃক্ষ মানব রোগ হয়েছে বাংলাদেশে একজনেরই – BBC বাংলা". BBC বাংলা (in Bengali). BBC. 30 January 2016. Retrieved 2016-01-30.
  24. ↑ Bangladesh's 'Tree Man' to undergo surgery, The Guardian , 31 January 2016.
  25. ↑ "Now I am well, says Bangladeshi Tree Man" . Retrieved 2016-07-11.
  26. ↑ "Hope for Bangladesh 'Tree Man' after 16 surgeries to remove growths". Al Arabiya. AFP. 10 January 2017.
  27. ↑ "'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.
  28. ↑ "Bangladesh 'Tree Man' wants hands amputated". Gulf News.
  29. ↑ "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.
  30. ↑ "Bangladeshi girl may be first female with 'tree man syndrome'". BBC News. 2017-01-31. Retrieved 2017-02-02.
  31. ↑ "Israeli doctors successfully operate on Gaza 'tree man'". Times of Israel. 2017-08-30. Retrieved 2017-08-30.
  32. ↑ "Extraño caso de "niña árbol" en Honduras". La Tribuna. October 23, 2018.
  33. ↑ "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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