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Tree man Syndrome

  • August 2018
DOI: 10.18689/mjiem-1000117
Authors:
Manjubala Dash at Mother Theresa Post Graduate and Research Institute of Health Sciences
Manjubala Dash
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78
Volume 2 • Issue 2 • 1000117Madridge J Intern Emerg Med.
ISSN: 2638-1621
Madridge
Journal of Internal and Emergency Medicine
Case Report Open Access
Tree man Syndrome
Manjubala Dash*
Professor, Department of Nursing, Mother Theresa Post Graduate & Research Institute of Health Sciences, India
Article Info
*Corresponding author:
Manjubala Dash
Professor
Department of Nursing
Mother Theresa Post Graduate & Research
Institute of Health Sciences
India
E-mail: manju_narayan@rediffmail.com
Received: August 8, 2018
Accepted: August 20, 2018
Published: August 27, 2018
Citation: Dash M. Tree man syndrome.
Madridge J Intern Emerg Med. 2018; 2(2): 78-79.
doi: 10.18689/mjiem-1000117
Copyright: © 2018 The Author(s). This work
is licensed under a Creative Commons
Attribution 4.0 International License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the
original work is properly cited.
Published by Madridge Publishers
Abstract
Tree man syndrome is an extremely rare condition more formally known as
Epidermodysplasia Verruciformis. Epidermodysplasia Verruciformis (EV, also called
Lewandowsky–Lutz dysplasia), colloquially known as tree man illness is an extremely
rare autosomal recessive genetic [1] hereditary skin disorder associated with a high risk
of carcinoma of the skin. It is characterized by abnormal susceptibility to human
papillomaviruses (HPVs) of the skin [2]. The resulting uncontrolled HPV infections result
in the growth of scaly macules and papules, particularly on the hands and feet. It is
typically associated with HPV types 5 and 8, [3] which are found in about 80% of the
normal population as asymptomatic infections, [4] although other types may also
contribute [3].
The condition usually has an onset of between the ages of one and 20, [5] but can
occasionally present in middle age [5]. It is named after the physicians who first
documented it, Felix Lewandowsky and Wilhelm Lutz (
de
) [6].
Keywords: Infections; Tree man; Syndrome; Epidermodysplasia; Scaly macules and
papules.
Causes
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. 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 [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. Generally, cutaneous
lesions are spread over the body, but some cases have only a few lesions which are
limited to one extremity [9], [10].
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 anti proliferative and differentiation-inducing effects.
ISSN: 2638-1621
Madridge Journal of Internal and Emergency Medicine
79
Volume 2 • Issue 2 • 1000117Madridge J Intern Emerg Med.
ISSN: 2638-1621
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.
Case Report
A young Bangladeshi girl with bark-like growths on her
face could be the first female afflicted by “tree man” syndrome,
doctors studying the rare genetic condition. Sahana Khatun,
10, has growths on her chin, ear and nose, but doctors at
Dhaka’s Medical College hospital are still conducting tests to
establish if she has the unusual skin disorder.
Fewer than half a dozen people worldwide have
epidermodysplasia verruciformis but none so far have been women,
said Samanta Lal Sen, the head of the hospital’s burn and plastic
surgery unit. “We believe she is the first woman,” Sen said.
Sahana Khatun
Abul Bajandar
Huge growths weighing five kilogrammes (11 pounds)
each had consumed the hands of 27-year-old
Abul Bajandar
,
the first recorded Bangladeshi to be suffering from the
disease.
References
1. Ramoz N, Rueda LA, Bouadjar B, Montoya LS, Orth G, Favre M. Mutations
in two adjacent novel genes are associated with epidermodysplasia
verruciformis. Nature Genetics. 2002; 32(4): 579–81. doi: 10.1038/ng1044
2. 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. The Journal of Experimental Medicine. 2008; 205
(1): 35-42. doi: 10.1084/jem.20071311. doi: 10.1084/jem.20071311
3. Orth G. Epidermodysplasia verruciformis: a model for understanding the
oncogenicity of human papillomaviruses. Ciba Foundation Symposium.
1986; 120: 157-74.
4. Antonsson A, Forslund O, Ekberg H, Sterner G, Hansson BG. The ubiquity
and impressive genomic diversity of human skin papillomaviruses suggest
a commensalic nature of these viruses. Journal of Virology. 2000; 74(24):
11636-41. doi: 10.1128/JVI.74.24.11636-11641.2000
5. Gül U, Kiliç A, Gönül M, Cakmak SK, Bayis SS. Clinical aspects of
epidermodysplasia verruciformis and review of the literature.
International Journal of Dermatology. 2007; 46 (10): 1069-72. doi:
10.1111/j.1365-4632.2006.03014.x
6. Lewandowsky-Lutz dysplasia: Who Named It?
7. Lazarczyk M, Favre M. Role of Zn2+ ions in host-virus interactions. Journal
of Virology. 2008; 82(23): 11486-94. doi: 10.1128/JVI.01314-08
8. Stigation. 122. American Society for Clinical Investigation. 3239-47.
doi:10.1172/JCI62949
9. Lowy DR, Androphy EJ, Warts. In Freedberg IM, Eisen AZ, Wolff K, et al.
Fitzpatrick’s Dermatology in General Medicine (6th ed). New York City:
McGraw-Hill. 2003; 2119-2131.
10. Pereira de Oliveira WR, Carrasco S, Neto CF, Rady P, Tyring SK. Nonspecific
cell-mediated immunity in patients with epidermodysplasia verruciformis
HPV. The Journal of Dermatology. 2003; 30(3): 203-9.
ResearchGate has not been able to resolve any citations for this publication.
Mutations in two adjacent novel genes are associated with Epidermodysplasia verruciformis
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Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by increased susceptibility to specific human papillomaviruses, the betapapillomaviruses. These EV-HPVs cause warts and increase the risk of skin carcinomas in otherwise healthy individuals. Inactivating mutations in epidermodysplasia verruciformis 1 (EVER1) or EVER2 have been identified in most, but not all, patients with autosomal recessive EV. We found that 2 young adult siblings presenting with T cell deficiency and various infectious diseases, including persistent EV-HPV infections, were homozygous for a mutation creating a stop codon in the ras homolog gene family member H (RHOH) gene. RHOH encodes an atypical Rho GTPase expressed predominantly in hematopoietic cells. Patients' circulating T cells contained predominantly effector memory T cells, which displayed impaired TCR signaling. Additionally, very few circulating T cells expressed the β7 integrin subunit, which homes T cells to specific tissues. Similarly, Rhoh-null mice exhibited a severe overall T cell defect and abnormally small numbers of circulating β7-positive cells. Expression of the WT, but not of the mutated RHOH, allele in Rhoh-/- hematopoietic stem cells corrected the T cell lymphopenia in mice after bone marrow transplantation. We conclude that RHOH deficiency leads to T cell defects and persistent EV-HPV infections, suggesting that T cells play a role in the pathogenesis of chronic EV-HPV infections.
Role of Zn2+ Ions in Host-Virus Interactions
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The involvement of Zn(2+) ions in the structure of ubiquitous protein zinc fingers gives this metal a particular position in the biology of the cell. ...
Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses
Article
Full-text available
Epidermodysplasia verruciformis (EV) is a genodermatosis associated with skin cancers that results from a selective susceptibility to related human papillomaviruses (EV HPV). Invalidating mutations in either of two genes (EVER1 and EVER2) with unknown functions cause most EV cases. We report that EVER1 and EVER2 proteins form a complex and interact with the zinc transporter 1 (ZnT-1), as shown by yeast two-hybrid screening, GST pull-down, and immunoprecipitation experiments. In keratinocytes, EVER and ZnT-1 proteins do not influence intracellular zinc concentration, but do affect intracellular zinc distribution. EVER2 was found to inhibit free zinc influx to nucleoli. Keratinocytes with a mutated EVER2 grew faster than wild-type keratinocytes. In transiently and stably transfected HaCaT cells, EVER and ZnT-1 down-regulated transcription factors stimulated by zinc (MTF-1) or cytokines (c-Jun and Elk), as detected with luciferase assays. To get some insight into the control of EV HPV infection, we searched for interaction between EVER and ZnT-1 and oncoproteins of cutaneous (HPV5) and genital (HPV16) genotypes. HPV16 E5 protein binds to EVER and ZnT-1 and blocks their negative regulation. The lack of a functional E5 protein encoded by EV HPV genome may account for host restriction of these viruses.
Epidermodysplasia Verruciformis: A Model for Understanding the Oncogenicity of Human Papillomaviruses
Article
The first evidence for the oncogenic potential of human papillomaviruses (HPVs) was obtained through the study of epidermodysplasia verruciformis (EV). This rare skin disease is characterized by disseminated, refractor, pityriasis versicolor-like lesions as well as flat wart-like lesions, and by the development of skin carcinomas in about 30% of the patients. EV is a multifactorial disease involving genetic, immunological and extrinsic (actinic) factors, in addition to infection with specific HPV types. A number of HPVs (at least 15 types) have been characterized in benign EV lesions. HPV DNA sequences are regularly detected in EV carcinomas but, in contrast to benign lesions, the types associated with cancers are usually restricted to HPV-5 and, less frequently, HPV-8, an HPV-5-related type. HPV-5 genomes are usually found as free monomeric or oligomeric DNA molecules in EV carcinomas, and frequently contain deletions. This is in contrast with HPV DNA sequences in genital cancers, which are often integrated into the host DNA. Evidence for the transcription of HPV-5 genomes in primary and metastatic EV carcinomas has recently been obtained. The available data indicate that HPV-5 and some HPV-5-related types have an oncogenic potential and play a role in the malignant transformation of EV lesions. Infection by these HPVs must be considered a major risk factor for the development of cancers in EV patients. EV HPV DNA sequences have only rarely been detected in premalignant or malignant lesions of the skin in the general population. This further stresses the role of genetic, immunological and extrinsic factors in the abnormal susceptibility of EV patients to a set of specific HPV types.
Nonspecific Cell-Mediated Immunity in Patients with Epidermodysplasia Verruciformis
Article
Epidermodysplasia verruciformis (EV) is a rare disease that usually begins in childhood and is characterized by a generalized infection by human papilloma virus (HPV), frequent associations with cutaneous carcinomas, and abnormalities of cell-mediated immunity (CMI). We studied nonspecific CMI in 13 patients with EV by bacterial skin tests, allergic reactions to dinitrochlorobenzene (DNCB), measurement of responses to phytohemagglutinin (PHA), and quantification of T lymphocytes and T lymphocytes subsets in peripheral blood. Impairment of CMI was manifested by the cutaneous anergy to a variety of common skin antigens and, by the reduction of the lymphocyte transformation to PHA. There were no correlation between the severity of cases and abnormalities of CMI in our patients, however; the impairment of CMI was lower in cases of short duration, suggesting that the impairment of CMI in EV might reflect a long period of disease.
Clinical aspect of epidermodysplasia verruciformis and review of the literature
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Epidermodysplasia verruciformis (EV), is an unusual genodermatosis characterized by persistent human papilloma virus infection with an autosomal recessive inheritance pattern. Clinically, it is characterized by flat wart-like lesions, scaly hypo- and hyperpigmented macules and/or patches, which resemble pityriasis versicolor, and development of early beginning nonmelanoma cutaneous carcinomas. The epidemiological and clinical features of seven cases with EV that have been followed up for 5 years were included in the study. Seven cases consisted of four males and three females. All seven cases were working outdoors. Three cases were the product of consanguineous marriages. The onset of the lesions was between the ages of 1-20 years (the average age was 9.29 years). The initial appearance of cutaneous tumors were between the ages 15-34 years (average age: 21.28 years). Six of seven cases had malignant cutaneous tumors, of which histopathological examination revealed squamous cell carcinoma (SCC). Three of our cases had radiotherapy previously for the existing SCCs. These cases had more early malignant transformations. Radiotherapy applied against the SCC previously, together with sunlight exposure may cause early malignant transformation of skin lesions and the destructive tumors.
Fitzpatrick's Dermatology in General Medicine
  • Jan 2003
  • 2119-2131
  • D R Lowy
  • E J Androphy
  • In Warts
  • I M Freedberg
  • A Z Eisen
  • K Wolff
Lowy DR, Androphy EJ, Warts. In Freedberg IM, Eisen AZ, Wolff K, et al. Fitzpatrick's Dermatology in General Medicine (6th ed). New York City: McGraw-Hill. 2003; 2119-2131.