Tree Man Syndrome

What is Tree Man Syndrome?

‘Tree Man syndrome’ is a rare, autosomal recessive genetic disorder, which affects deep skin tissues. The immune system weakness increases the susceptibility towards human papillomavirus (HPV) infection in the affected individual in their early phase of life.

Clinically ‘Tree Man syndrome’ is also known as Epidermodysplasia verruciformis1,2.

Tree Man Syndrome 1


The frequency of ‘Tree Man syndrome’ is rare. The theoretical information showed almost 95 cases till diagnosed ‘Tree Man syndrome’ from the region of Poland, Eastern Europe, and Latin America, no history yet from the United States. In Bangladesh, might be first girl child detected with ‘Tree Man syndrome’. Although the syndrome is a universal disorder and can occur at any races. This ailment is also not gendered specific, both the gender can affect.

‘Tree Man syndrome’ can usually occur at childhood. The onset of the syndrome may be manifested as a congenital disorder (almost 7.5% cases), or at early childhood in the age between 5 to 11 years (almost 61.5% cases), or at adolescent age (almost 22.5% cases).

The association of ‘Tree Man syndrome’ and malignancy is quite common. The development of malignant tissue usually occurs during the fourth and fifth decades of life and approximately 30% of 60% ‘Tree Man syndrome’ converts to malignant changes2,3.


The pathophysiology of ‘Tree Man syndrome’ is related to faulty cell-mediated immunity, with the illumination of mutations in EVER1 and EVER2 genes.  Almost 25% of ‘Tree Man syndrome’ patients have deficit mutations in EVER1 and EVER2.

However, the involvement and the exact mechanism of EVER1 and EVER2 genes are not yet understood clearly. In addition, CD8+ T-cell lymphocytopenia also identified in some ‘Tree Man syndrome’ cases. Furthermore, research is required for complete understanding of the pathophysiology of ‘Tree Man syndrome’1,2.


‘Tree Man syndrome’ symptoms include widely spread skin rashes with flat-to-papillomatous, wart-like lesion and the skin in upper and lower limb, trunk, the face has typical reddish-brown pigmented plaques. The more extensive description can classify ‘Tree Man syndrome’ into two types:

Type 1:

Wart-like lesion has a flat surface and looks like plane warts. The flat-topped papules are pigmented with light pink to violet in color. In some locations, plaques are formed by amalgamations of papules. The plaques may have scaly surfaces with irregular edges and in reddish brown color. But some plaques may be hyperpigmented or hypopigmented.

Type 2:

Some lesion of ‘Tree Man Syndrome’ are seborrhoeic keratoses or verrucous like. Mostly sun-exposed skin get affected. These skin lesions are brown colored and have more susceptibility to develop malignancy than flat surfaced ‘Tree Man Syndrome’ warts.

However, flat surfaced warts can develop in sun-exposed body parts like in face, ear lobe, hand, and feet, whereas, plaque-like lesions may develop on the neck, trunk, upper part of hands and legs. In some patients, lesions can spread to palms, armpits, soles and external genital organs. At the initial stage, warts appear as a small cluster, but later it combined with few hundred warts 1,2,4.


  • ‘Tree Man syndrome’ is a non-curable progressive disease and extends throughout the lifespan. In some cases, after the development of lesions, their growth may be stagnant for few years and remain unchanged. The fetal outcome usually associated with malignant cells like squamous cell carcinoma,  intraepidermal carcinoma, adnexal tumors and basal cell carcinoma development.
  • In the present situation, no treatment available for prevention of ‘Tree Man syndrome’. The ‘Tree Man syndrome’ can be managed by medical and surgical interventions. Apart from these, awareness, counseling and regular surveillance is required especially for immunocompromised individuals.
  • To control the growth of the ‘Tree Man syndrome’ tumor, sun protection is very important.
  • Different less invasive treatments like electrosurgery, cryotherapy with liquid nitrogen,  and laser ablation technique can apply for removal of warts.
  • Different chemotherapeutic drugs like fluorouracil or others may prescribe orally or topical application.
  • Oral retinoids are prescribed for pre-malignant lesions to restrict its conversion to malignancy.
  • Immunotherapy is prescribed to develop immunity.
  • interferon may be effective for patients who have an intact immune system.
  • Imiquimod and cimetidine may be used for patients to control the malignancy.
  • Skin grafts, excision and defect reconstruction are different surgical intervention provides a better outcome1,5,6.


In the initial stage of ‘Tree Man syndrome’, a numerous number of noninvasive tumor growth occur. Fatality related to ‘Tree Man syndrome’ is rare. But the tumor growth associated with ‘Tree Man syndrome’ is progressive in nature and evolve throughout the life cycle. Metastasizing of ‘Tree Man syndrome’ tumor provides fatality outcome.

Invasive nature of metastatic tumor occasionally arises from conjunctiva and progress to squamous cell carcinoma. Approximately, one-third of the ‘Tree Man syndrome’ affected patients develop Malignant skin tumors during 4th to 5th decades of life.

The cancer cells are local and very rarely spread to other organs. Without treatment, the invasive, metastasized ‘Tree Man syndrome’ tumor is locally destructive2.


  1. Ilteris Murat Emsen,  M Esref Kabalar, Epidermodysplasia verruciformis: An early and unusual presentation; Can J Plast Surg. 2010 Spring; 18(1): 21–24; Retrieve from
  2. Anthony A Gaspari (2016); Epidermodysplasia Verruciformis; Retrieve from
  3. This Could Be This First Female With “Tree Man Syndrome”; Retrieve from
  4. Vanessa Ngan, Staff Writer, 2006; Epidermodysplasia verruciformis; Retrieve from
  5. Anadolu R, Oskay T, Erdem C, Boyvat A, Terzi E, Gürgey E. Treatment of epidermodysplasia verruciformis with a combination of acitretin and interferon alfa- 2a. J Am Acad Dermatol. 2001;45:296–9.
  6. 9. Hu W, Nuovo G, Willen M, Somach S. Epidermodysplasia verruciformis in two half brothers with HIV infection. J Cutan Med Surg.

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