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) 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]

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, 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

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

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

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' 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

Ion Toader

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

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:

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 ]

Omar Tamim

In 2013, one case of epidermodysplasia verruciformis was reported in Iraq. No treatment was given since the condition was initially misdiagnosed.

Abul Bajandar

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]

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. [28]

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. [29]

Cristhél Suyapa Martínez

In October 2018, a five-year-old girl in Honduras, Cristhél Suyapa Martínez, was diagnosed with the condition. [30]

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. [31]

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 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 cancerous 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, or verruca vulgaris, 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">Molluscum contagiosum</span> Viral infection of the skin

Molluscum contagiosum (MC), sometimes called water warts, is a viral infection of the skin that results in small raised pink lesions with a dimple in the center. They may become itchy or sore, and occur singularly or in groups. Any area of the skin may be affected, with abdomen, legs, arms, neck, genital area, and face being the most common. Onset of the lesions is around seven weeks after infection. They usually go away within a year without scarring.

<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">Actinic keratosis</span> Skin disorder

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. These growths are more common in fair-skinned people and those who are frequently in the sun. They are believed to form when skin gets damaged by UV radiation from the sun or indoor tanning beds, usually over the course of decades. Given their pre-cancerous nature, if left untreated, they may turn into a type of skin cancer called squamous cell carcinoma. Untreated lesions have up to a 20% risk of progression to squamous cell carcinoma, so treatment by a dermatologist is recommended.

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

Keratoacanthoma (KA) is a common low-grade rapidly-growing skin tumour that is believed to originate from the hair follicle and can resemble squamous cell carcinoma.

<span class="mw-page-title-main">Pyogenic granuloma</span> Vascular tumor on both mucosa and skin

A pyogenic granuloma or lobular capillary hemangioma is a vascular tumor that occurs on both mucosa and skin, and appears as an overgrowth of tissue due to irritation, physical trauma, or hormonal factors. It is often found to involve the gums, skin, or nasal septum, and has also been found far from the head, such as in the thigh.

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

Angiokeratoma is a benign cutaneous lesion of capillaries, resulting in small marks of red to blue color and characterized by hyperkeratosis. Angiokeratoma corporis diffusum refers to Fabry's disease, but this is usually considered a distinct condition.

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">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">Kaposi's sarcoma</span> Cancer of the skin, integumentary lymph nodes, or other organs

Kaposi's sarcoma (KS) is a type of cancer that can form masses in the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limited area, or may be widespread. Depending on the sub-type of disease and level of immune suppression, KS may worsen either gradually or quickly. Except for Classical KS where there is generally no immune suppression, KS is caused by a combination of immune suppression and infection by Human herpesvirus 8.

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". It originally was a disease of only losing eyelashes but it currently is the loss of both eyelashes and eyebrows. Eyebrows and eyelashes are both important in the prevention of bacteria and other foreign objects from entering the eye. A majority of patients with madarosis have leprosy, and it was reported that 76% of patients with varying types of leprosy had madarosis.

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

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

<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. The lesions have a typical dysplastic histology and are generally considered benign, although a small percentage will develop malignant characteristics.

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. ↑ 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. 1 2 "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. ↑ "Bangladeshi girl may be first female with 'tree man syndrome'". BBC News. 2017-01-31. Retrieved 2017-02-02.
  29. ↑ "Israeli doctors successfully operate on Gaza 'tree man'". Times of Israel. 2017-08-30. Retrieved 2017-08-30.
  30. ↑ "Extraño caso de "niña árbol" en Honduras". La Tribuna. October 23, 2018.
  31. ↑ "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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