Epidermodysplasia verruciformis

Epidermodysplasia verruciformis
File:File:World's 4th a Tree Man.jpg
Synonyms	Lewandowsky–Lutz dysplasia, treeman syndrome
Pronounce
Field	Dermatology
Symptoms
Complications
Onset
Duration
Types
Causes	Genetic
Risks
Diagnosis
Differential diagnosis
Prevention
Treatment
Medication
Prognosis
Frequency
Deaths

Epidermodysplasia verruciformis (EV), also known as treeman syndrome, is an extremely rare autosomal recessive<ref name="Ramoz 2002">,

 Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis, 
 Nature Genetics, 
 
 Vol. 32(Issue: 4),
 pp. 579–81,
 DOI: 10.1038/ng1044,
 PMID: 12426567,</ref> hereditary skin disorder associated with a high risk of skin cancer. It is characterized by abnormal susceptibility to human papillomaviruses (HPVs) of the skin.<ref name="EVER HPV">, 
 Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses, 
 The Journal of Experimental Medicine, 
 
 Vol. 205(Issue: 1),
 pp. 35–42,
 DOI: 10.1084/jem.20071311,
 PMID: 18158319,
 PMC: 2234378,</ref> The resulting uncontrolled HPV infections result in the growth of scaly macules and papules resembling tree bark, particularly on the hands and feet. It is typically associated with HPV types 5 and 8,<ref name="HPV types">Orth G, 
 Epidermodysplasia verruciformis: a model for understanding the oncogenicity of human papillomaviruses, 
 Ciba Foundation Symposium, 
 1986,
 Vol. 120,
 pp. 157–74,
 DOI: 10.1002/9780470513309.ch11,
 PMID: 3013521,</ref> which are found in about 80% of the normal population as asymptomatic infections,<ref name="commensal">, 
 The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses, 
 Journal of Virology, 
 
 Vol. 74(Issue: 24),
 pp. 11636–41,
 DOI: 10.1128/JVI.74.24.11636-11641.2000,
 PMID: 11090162,
 PMC: 112445,</ref> although other types may also contribute.<ref name="HPV types"/>

The condition usually has an onset of between the ages of one and 20<ref name=Gul>,

 Clinical aspects of epidermodysplasia verruciformis and review of the literature, 
 International Journal of Dermatology, 
 
 Vol. 46(Issue: 10),
 pp. 1069–72,
 DOI: 10.1111/j.1365-4632.2006.03014.x,
 PMID: 17910717,</ref> but it can occasionally be present in middle age.<ref name=Gul /> The condition is also known as Lewandowsky-Lutz dysplasia, named after the physicians who first documented it, Felix Lewandowsky and Wilhelm Lutz.<ref>Lewandowsky–Lutz dysplasia: Who Named It?</ref>

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.

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.

Generally, cutaneous lesions are spread over the body, but some cases have only a few lesions which are limited to one extremity.<ref>,

 Fitzpatrick's Dermatology in General Medicine, 
 6th edition, 
 New York City:McGraw-Hill, 
 2003, 
  
  
 ISBN 978-0-07-138076-8, 
  
  
  
 Pages: 2119–2131,</ref><ref>, 
 Nonspecific cell-mediated immunity in patients with epidermodysplasia verruciformis HPV, 
 The Journal of Dermatology, 
 
 Vol. 30(Issue: 3),
 pp. 203–9,
 DOI: 10.1111/j.1346-8138.2003.tb00372.x,
 PMID: 12692356,
 
 
 Full text,</ref>

Genetics

The cause of the condition is an inactivating PH mutation in either the EVER1 or EVER2 genes, which are located adjacent to one another on chromosome 17.<ref name="Ramoz 2002" /> 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.<ref name="EVER Zn">,

 Role of Zn2+ ions in host-virus interactions, 
 Journal of Virology, 
 
 Vol. 82(Issue: 23),
 pp. 11486–94,
 DOI: 10.1128/JVI.01314-08,
 PMID: 18787005,
 PMC: 2583646,</ref>

Other genes have also rarely been associated with this condition. These include the ras homolog gene family member H.<ref name=Crequer2012>Crequer, Amandine,

 Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections, 
 The Journal of Clinical Investigation, 
 
 Vol. 122(Issue: 9),
 pp. 3239–3247,
 DOI: 10.1172/JCI62949,
 PMID: 22850876,
 PMC: 3428089,</ref>

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.

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.

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.

Notable cases

Ion Toader

In March 2007, a Romanian man named Ion Toader was diagnosed with this condition.<ref> Allen, Mark. Missionary encounters extremely bizarre skin condition in Eastern Europe(link). {{{website}}}. WFMU. 12 March 2007.

</ref> 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. ^{(December 2007)}

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 34-year-old Indonesian man named Dede Koswara with a similar disease appeared on the Internet.<ref> ,

 The man who looks like a tree Full text, 
 Metro, 
  
 22 November 2007,

</ref> 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".<ref>

Half Man Half Tree(link). {{{website}}}. Discovery Channel.

</ref> On August 12, 2008, Koswara's story was the subject of an ABC's Medical Mystery episode entitled "Tree Man".<ref>

"Tree Man" Medical Mystery(link). {{{website}}}. ABC News. 15 August 2008.

</ref>

On 26 August 2008, Koswara returned home following surgery to remove 6 kg (13 lb) of warts from his body.<ref name=warts>,

 Indonesia's 'tree man' comes home after treatment, 
 Los Angeles Times, 
 
 
 
 
 
 
 
 Full text,</ref> 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.<ref name=warts /> The surgery was documented by the Discovery Channel and TLC in the episode "Treeman: Search for the Cure". ^{(August 2009)}

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.<ref>

Nathalia, Telly,

 'Tree man's' warts growing again Full text, 
 The Australian, 
  
 20 December 2008,

</ref> 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. ^{(March 2016)}

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. ^{(December 2017)}

Aged 42, Koswara died on 30 January 2016, around 03:30 Western Indonesia Time, at Hasan Sadikin Hospital, Bandung, from the complications related to his condition.<ref> Sabtu,

 Dede Koswara Embuskan Nafas Terakhir, Ini Penyebab Kematian 'Manusia Akar' Bandung Full text, 
 , 
  
 30 January 2016,

</ref>

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.

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.<ref>

Rare disease: DMCH to form medical board tomorrow(link). The Daily Star.

2016-01-30.

Accessed 2016-01-30.

</ref><ref>

বিরল এই বৃক্ষ মানব রোগ হয়েছে বাংলাদেশে একজনেরই - BBC বাংলা(link). BBC বাংলা. BBC.

Accessed 2016-01-30.

</ref> 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.<ref>Bangladesh's 'Tree Man' to undergo surgery, The Guardian, 31 January 2016.</ref><ref>

Now I am well, says Bangladeshi Tree Man(link). {{{website}}}.

Accessed 2016-07-11.

</ref><ref> ,

 Hope for Bangladesh 'Tree Man' after 16 surgeries to remove growths Full text, 
 Al Arabiya, 
  
 10 January 2017,

</ref> 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 conditioned had significantly worsened and spread to his feet. He will reportedly need five to six operations to get the condition back under control. <ref>

'Big mistake for me to leave': Man's 'tree man' condition returns worse than before after interrupting treatments(link). {{{website}}}.

</ref> In June 2019 he has requested to get his arms amputated as the pain is unbearable.<ref> ,

 Bangladesh 'Tree Man' wants hands amputated Full text, 
 Gulf News,

</ref>

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.<ref> ,

 Bangladeshi girl may be first female with 'tree man syndrome' Full text, 
 , 
  
 2017-01-31, 
  
  
 Accessed on: 2017-02-02.

</ref>

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.<ref> ,

 Israeli doctors successfully operate on Gaza 'tree man' Full text, 
 , 
  
 2017-08-30, 
  
  
 Accessed on: 2017-08-30.

</ref>

Cristhél Suyapa Martínez

In October 2018, a five-year-old girl in Honduras, Cristhél Suyapa Martínez, was diagnosed with the condition.<ref>

Extraño caso de "niña árbol" en Honduras(link). {{{website}}}. La Tribuna. October 23, 2018.

</ref>

Further reading

• ,

 The virus of epidermodysplasia verruciformis: electron microscopic and fluorescent antibody studies, 
 The Journal of Investigative Dermatology, 
 
 Vol. 65(Issue: 3),
 pp. 324–30,
 DOI: 10.1111/1523-1747.ep12598388,
 PMID: 808576,

• ,

 Ein Fall einer bisher nicht beschriebenen Hauterkrankung (Epidermodysplasia verruciformis), 
 Archiv für Dermatologie und Syphilis, 
 
 Vol. 141(Issue: 2),
 pp. 193–203,
 DOI: 10.1007/BF01938833,
 
 
 
 Full text,

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