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Research 2 - Vitiligo Repigmentation by Follicular Unit Grafting


The result of this study was published in Hair Transplant Forum International ( Vol 20:2, Mar / Apr 2010 )

Before Transplant After Transplant
Before hair transpalnt into eyebrows After grafting


Vitiligo Repigmentation by Follicular Unit Grafting

Vitiligo affects about 1% of the world's population including individuals of all ethnic groups and both genders. This skin condition was reported to be an acquired cutaneous achromia probably determined by an autosomal gene (1). As hairs within a vitiliginous patch of skin are often depigmented, the autoimmune injury must involve both the epidermal and follicular melanocytes (2).

Vitiligo on exposed areas may not be amendable to cosmetic cover-up. Treatment is indicated when the psychological well being of the patient is severely affected. When less than 10% of the body surface is affected, repigmentation can be considered (3). Over the years different medical and surgical modalities have been reported in an attempt to restore melanocytes at the vitiliginous sites (4).

Surgical techniques are usually offered to those with refractory but stable vitiligo that has no new lesions in the past 2 years. Currently used modalities include cosmetic tattooing or micropigmentation, regional dermabrasion, transplantation of blister tops, autologous cultured melanocyte grafting, autologous non-cultured epidermal cell suspension, and single hair transplantation.


Single hair grafting

 Single hair grafting in treating vitiligo was described by Na in 1998 (5). 21 patients with a mean age of 23.4 and a mean disease duration of 7.7 years were recruited in the study. In the occiput a 1cm strip was harvested, slivered, and then divided into many single hair grafts using No. 20 surgical blades. The whole follicle was used for hair-bearing areas, while only the upper two-third was used for glabrous areas.

All grafts were inserted using the Choi implanters. The density of transplant was not mentioned in the study. Follow up was from one to three years. Different patterns of repigmentation were observed in two groups :

  • Localized / segmental vitiligo –14 out of 17 patients (81%) developed peri-follicular repigmentation. The area ranged from 2-10mm (average 3mm) in diameter
  • Generalized vitiligo – only 1 in 4 (25%) developed a peri-follicular repigmentation 3mm in diamete
In this study all transplanted hair retained pigmentation at 12 months follow up. Five patients (23.8%) had repigmentation of depigmented hair in the vitiliginous areas. Single hair grafting however has not enjoyed popularity at that time as hair dissection was “tedious and time consuming”, and the number of donor hairs was “limited” as described by the authors. When stereo-microscopic graft dissection and mega-session have become a norm in today hair restoration surgery, should this technique be re-considered ?


Case History

A 45 years old Asian male presented to our clinic in August 2001. He requested eyebrow transplantation to area affected by Vitiligo. He had no other medical condition and was not on any regular medication. There has been no change in the lesion for many years.

On examination there was a patch of vitiliginous skin along the medial two-third of the left supraorbital ridge. It was rectangular in shape and measured about 1cm X 3cm with an area of 3 sq.cm. Depigmented hairs were found in this area. The density of the eyebrow was low in the medial one-third.

A donor strip 0.8 X 3 cm was removed. Only pigmented hairs were selected and the 2-hairs and 3-hairs follicular units were spitted into a total 169 one-hair grafts. 21G needles were used for “stick and place”. 122 grafts were transplanted to the medial two-third of the left side amongst the existing depigmented hairs. 47 grafts were added to the upper margin of the right eyebrow to create a symmetrical look. Postoperative progress was uneventful.


Results

 On follow up in January 2008 (after 7 years) there was a complete remission of the localized vitiligo. No new lesion was observed elsewhere. The original depigmented eyebrow remained depigmented. Although the transplanted hairs retained most of the density, at least half had lost their color.

Patient rejected the proposal of dyeing the eyebrows as cosmetic cover-up. A second session is planned to replace the depigmented hair one by one using the technique of follicular unit extraction (FUE).


Comments

Melanocytes are reported to be located in 3 parts of the human hair follicles (6):
  • In the hair bulb epithelium, around the upper half of the dermal papilla
  • In the basal layer of the infundibulum
  • In the outer root sheath (ORS)
location of melanocytes


The hair bulb melanocytes donate melanin to the hair cortex and determine the color of the human hair. Melanogenesis continues throughout the anagen and then ceases with the onset of catagen. Hair bulb melanocytes are also believed to be interchangeable with epidermal melanocytes in donating melanin to the cortical keratinocytes.
The outer root sheath melanocytes, in a smaller numbers, contain no melanin and are believed to form a melanocyte reservoir in the skin. Their potential to be reactivated; to proliferate and migrate to the epidermis; to induce remission and repigmentation; had been demonstrated by Kim and Choi (7) and Cui et al (8).

In this case the bulb melanocytes were vulnerable to autoimmune injury in vitiligo. There were three interesting findings in this case report :
  • The vitiliginous skin gained colour
  • The transplanted hairs lost color
  • No change in the depigmented hair
Spontaneous remission seems too much a co-incidence. The followings were proposed to explain the phenomenon :
  • The melanocytes of the transplanted hair follicles were injured by the residing immunological effect. Though the disease remained silent for years it was ready to attack any invading melanocytes
  • The hair follicles also carried a reservoir of melanocytes unaffected by the immunological injury, and capable of inducing remission in the vitiliginous skin
  • These reservoir melanocytes were more catered for the epidermis rather than the hair follicles.
As observed in this case they are a different entity to the bulb melanocytes and capable of escaping the immunological injury after transplantation. If the amount of these melanocytes is proportional to the thickness of the ORS, they should be most abundant in the middle third of the follicle (isthmus), less in the lower third (hair bulb), and none in the upper third (infundibulum) (9).

Sardi reported his use of hair follicle grafting in treating vitiligo but commented that “one of the problems that arise is that repigmentation may not be obtained” (10). However he was only grafting the upper one-third to upper half of the follicles. When Na was using the entire follicles or the upper two-third a better result was observed. There are many advantages to re-consider the use of single hair grafting (5) :
  • The scalp provides an easily assessable source of melanocytes
  • A single hair contains more melanocytes than normally pigmented glabrous, usually gluteal area, and skin
  • A cobblestone hypertrophic scar on recipient site does not appear because of a small bored needle is used
  • The method is advantageous when hair density is needed in the recipient site
  • This modality can be easily applied to a small area of vitiligo
  • The method does not produce postoperative hyperpigmentation in the grafted sites as does autologous suction blister grafts
  • It can be performed in the eyelash area or angle of the mouth where other surgical methods are difficult
  • Add-on or touch-up repigmentation can be achieved by inserting grafts into selected areas
  • The overall complications and side-effects were minimal. The donor scar can easily covered by existing hair and unnoticeable when compared to the use of gluteal skin
  • Sophisticated and expensive equipment are not required.
  • The procedure can be performed in a clinic by a well trained hair surgeon
With the advance in Hair Restoration Surgery a large number of grafts can be harvested, prepared, and inserted within a short period of time. Follicles transection is now minimized by direct visualization in strip dissection and the use of microscopes in grafts preparation 13. Donor scar is minimal if not invisible by using FUE 14 or the Trichophytic Closing Technique (15).

The whole graft is used for hair-bearing areas. For glabrous areas only the middle one-third should be used with the hair shaft removed to avoid foreign body reaction. Removal of the hair bulbs may help to reduce hair growth. Since the stem cells at the bulge are also capable of differentiation, there is always a risk of ingrown hair and folliculitis. By discarding the upper one-third which contains minimal ORS melanocytes, the path of migration to the epidermis is shortened. Such manipulation of the follicles becomes easier when performed under microscopic magnification.

Grafts can be inserted and evenly distributed using Choi implanters 16 or forceps. Most hair surgeons can transplant an average of 35 follicles per sq.cm. Density up to 50-60 had been reported in centers specialized in mega-sessions.
According to Na the average peri-follicular repigmentation is 3mm in diameter and 0.07 sq.cm in area. Theoretically 15 follicles are sufficient to repigment an area of one sq.cm. This density can be transplanted in the first session. Based on this calculation 1,000 grafts can cover an area of 65 sq.cm. Some hair transplant clinic can manage 3,000 to 4,000 grafts in a single day session. A minimal of 8 months is needed before commenting on the final outcome. Any emerging hair can be ablated by laser (17).

Further sessions may be considered if there is only partial repigmentation, or to successively cover a large area. Most patients can donate up to a total 10,000 grafts. A minimal of 6,000 donor grafts can still be mobilized from a Norwood Class V patient. In order to achieve more rapid repigmentation, the technique can be combined with narrowband UVB, PUVB, or topical corticosteroid therapies (12).

Clinical trial using this modified treatment modality is needed. Also a few technical details need to be clarified :
  • What is the optimal depth for inserting the segmented follicles?
  • Would including the upper one-third of the follicle reduce the incidence of ingrown hair by providing an exit on the epidermis?
  • Would an intact 2 hair-FU achieve a better repigmentation than splitting it into two 1 hair-graft? If a lesser number of 2 or 3 hair-FUs can achieve comparable result, time can be saved in preparing grafts and incisions?

Conclusion

Single hair grafting can be considered in the treatment of localized and segmental vitiligo in the exposed areas. This case study suggested that the different melanocytes carried by the hair follicle have different immunological response to vitiligo. Grafting should include the middle one-third of the hair follicle which contains the maximum amount of ORS melanocytes. The procedure is simple according to today standard and can be performed in any hair surgeon’s office.


Reference

1. Rodney Dawber, Diseases of the Hair and Scalp, 3rd Edition Blackwell Science, page 411

2. Rodney Dawber, Hair and Scalp Disorders, Lippincott Company, page 239

3. Lim H, Hexsel C. Vitiligo: To Treat or Not To Treat. Editorial, Arch Dermatology. Vol 143;May 2007; 643-646

4. Tegta G, Parsad D, Majumdar S, Kumar B. Efficacy of Autologous Transplantation of Noncultured Epidermal Suspension in Two Different Dilutions in the Treatment of Vitiligo. International Journal of Dermatology 2006;45;106-110

5. Na GY, See SK, Choi SK. Single Hair Grafting for the Treatment of Vitiligo. J Am Acad Dermatol 1998; 38;580-84

6. Elise Olsen, Disorders of Hair Growth – Diagnosis and Treatment, 2nd Edition McGraw-Hill, Chapter 3

7. Kim JC, Choi YC. Regrowth of Grafted Human Hair After Removal of the Bulb. Dermatol Surg 1995;21;312-3

8. Cui J, Shen L, Wong G. Role of Hair Follicles in the Repigmentation of Vitiligo. J Invest Dermatolgy 1991;97;410-6

9. Walter Unger, Hair Transplantation, 4th Edition; page 29

10. Sardi Jose. Surgical Treatment for Vitiligo Through Hair Follicle Grafting: How to Make it Easy. Dermatological Surgery 2001;27:685-686

11. Mulekar S. Long-term follow-up study of 142 patients with vitiligo vulgaris treated by autologous, non-cultured melanocyte-keratinocyte cell transplantation. International Journal of Dermatology 2005;44;841-845

12. Rusfianti M, Wirohadidjodjo Y. Dermatological techniques for repigmentation of Vitiligo. International Journal of Dermatology 2006;45;411-417

13. Cooley J, Vogel J. Follicle trauma and the role of the dissecting microscope in hair transplantation. A multicenter study. Dermatol Clin. 1999;April;17(2):307-12,vii; discussion 312-3

14. Gökrem S, Baser NT, Aslan G Follicular unit extraction in hair transplantation: personal experience. Ann Plast Surg. 2008 Feb;60(2):127-33

15. Marzola M. Trichophytic Closure of the Donor Area. International Hair Forum. Jul-Aug 2005; 15(4).

16. Choi YC, Kim JC. Single Hair Transplantation using the Choi Hair transplanter. J Dermatol Surg Oncol.1992 Nov;18(11):945-8

17. Vittorio C, Lehrer M. Laser Hair Removal. Facial Plastic Surgery 2003;10(1);131-136

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