Surgical modalities of treatment in vitiligo

Non-Grafting techniques

The techniques include chem-abrasion, dermabrasion, laser and light therapies, needling, and excimer. In these methods, the lesion is therapeutically wounded, thus melanocytes proliferate at the periphery and migrate to repopulate the depigmented area. Also, there is an influx of stimulatory cytokines.^[13] Dermabrasion in addition helps in the penetration of ultraviolet radiation, which then stimulates the melanocytes.^[14]

Camouflage tattooing

In this, there is introduction of artificial pigment into the mid dermis in the depigmented patch. This has a poor color match and at times imparts a bluish tinge.^[15] A chalazion clamp can be utilized for providing stretch and stability, while one performs tattooing on the lips.^[16]

Grafting techniques

Autologous grafting can be further divided into those techniques where tissue is transferred and those in which cells are transferred. Cells can be transferred as is or can be cultured to increase the number of melanocytes to help in wider area of coverage.^[17] These methods were started in the early 1960 and since then have refined further. The basic principle in vitiligo grafting surgery is to transplant the graft as a whole in tissues grafts or through cellular suspension (cultured or non-cultured) where the recipient area can be increased. The donor to recipient ratio is briefly summarized in Table 1. In most of the techniques, there is a necessity to prepare the recipient site in order to promote the uptake of the transferred melanocytes. This can be done by various methods as outlined in Table 2. The subsequent uptake of melanocytes and thus the final pigmentation achieved has been seen to vary depending on the technique.^[18]

Punch graft

In this technique, small punches are harvested from normally pigmented skin and are transplanted into the depigmented recipient area [Figure 2]. This method relies heavily on the transplanted graft to stimulate pigment production in the surrounding depigmented skin. In a recent meta-analysis comparing various surgical methods, > 90% pigmentation was seen in 45.76% of patients after punch grafting.^[19] Since most dermatologists are well versed with punch biopsy technique, it is easy to learn and perform with minimal additional equipment to be purchased. It is especially useful in areas like the palms and soles, where there is a doubtful recipient bed and the nipple areola with its irregular contour. Care should be taken that recipient punches are smaller than the donor punches by approximately 0.5 mm. A unique side effect of this technique is the cobble stoned appearance. This can be prevented by taking small size punches (1–1.5 mm), grafts kept at-least 5 mm apart, with thinner grafts and the upper surface at the level of the recipient skin. The depth of the donor graft can be minimized by injecting local anesthetic at the junction of upper and mid dermis.^[20] It was recently seen in a study on vitiligo patches in rats that irrespective of the orientation of the transplanted donor graft, the repigmentation was good.^[21]

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Figure 2:

Punch grafting (a) patch of vitiligo (b) punch grafting after 1 week and (c) after 6 months showing almost complete repigmentation.

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Suction blister epidermal grafting [Figure 3].

Falabella had developed this novel technique, wherein a negative pressure is created of –200 to –500 mm Hg with the help of a syringe at the donor skin site. This causes a split at the dermoepidermal junction and forms a blister. This is deroofed and taking care as to which side is epidermal and which one is dermal, is transplanted into a prepared recipient site. This has shown to achieve excellent pigment match. However, this is much more difficult to learn, is not feasible in cold weathers, not suitable for large areas, and patient has to wait for a long time until the blister forms.^[22] A recent study found SBEG superior to the punch grafting over acral areas and bony prominences.^[23] Modifications are available to speed up the formation of blister, these include heat application, normal saline injected intradermally, use of smaller syringes, and greater negative pressure.^[24] An exploitation of alternative system of medicine includes the use of Hijama cups for the creation of negative pressure and blister.^[25] These are used in cupping therapy and consist of cups ranging from 2 to 7 cm with a provision for the attachment of a syringe to the valve on top of each.

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Figure 3:

Suction blister technique with (a) negative pressure applied with disposable syringes and (b) suction blisters after 4 hours.

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Split-skin grafting

In the early 1970s, Dr. P.N. Behl demonstrated efficient repigmentation of vitiligo skin lesion with the help of split thickness skin graft.^[26] Although initially thicker grafts of 0.1–0.2 mm were used, the trend now is to use ultra-thin grafts of 0.08 mm.^[27] It must be kept in mind that the graft shrinks when transferred to the recipient site and thus must be 10–20% larger than the defect to be covered. Larger lesions can be covered by meshing the graft, which allows for expansion.

Seed grafts/Smash grafts

This is a variant of ultrathin and split thickness skin graft, wherein the sheets of tissue are minced to fragments less than 1 mm with the help of sterile scissors. This paste is applied to the prepared recipient site. The smaller the particles, the better will be the result.^[28] A modification of this is to insert the minced grafts with the help of needling into the dermis. The results of this novel method were better than conventional dermabrasion alone.^[29]

Flip top grafting

A hinge of tissue is raised in the epidermis at the recipient site and small pieces of donor tissue are slid underneath. This provides a cheap, natural yet effective dressing. It also serves as a window, allowing one to see the extent of repigmentation and thus determine the success of the procedure.^[30]

Hair follicle grafting

This method is akin to follicular unit extraction or strip follicular transplant of hair transplant, wherein hair follicles are harvested and transplanted into another area. The donor site is usually the hair on the occipital area of scalp. The spacing between the transplanted hair is usually 5–10 mm.^[31] Modifications of this technique include eyelash transplantation for leucotrichia and vellus hair transplantation.

Cultured melanocyte transplantation

In this method, a split thickness skin graft is harvested, and melanocytes are separated. Their numbers are increased with the help of cellular culture techniques to cover a larger area. The donor:recipient ratio is 1:60. The melanocytes can also be co-cultured with keratinocytes. Co-culturing with keratinocytes is advantageous due to the presence of melanocyte stimulatory growth factors secreted by them.^[32] Although this technique dramatically increased the area that can be covered, the cost is higher.^[33]

Non-cultured epidermal cell suspension (NCES)

The pioneer of this method was Gauthier, which was similar to the cultured melanocyte transplantation.^[34] However, it can be performed even in places without cell culture facilities. It however has a lower donor to recipient ratio of 1:5 to 1:10.^[35] This does not limit its application as the ratio is still quite large and a greater number of donor sites can be used if one needs to cover larger areas. The trypsinization of harvested split thickness graft can be done by cold or by warm method to separate the cells. In the conventional cold method, the trypsin acts for 18 hours, on the tissue at a temperature of 4°C. This was modified by Olsson and Juhlin in 1998, in which the digestion time was cut down to 60 minutes at a temperature of 37°C.^[36] Warm trypsinization, while quicker, has shown to be inferior to cold one, with a lower yield of viable cells.^[37] Newer methods such as room temperature trypsinization has shown efficacy comparable to other methods.^[38]

There has been various modification of this technique, such as addition of hyaluronic acid to increase the viscosity (Van Geel et al.),^[39] substitution of melanocyte culture media with phosphate buffered saline (Holla et al.).^[40] Platelet-rich plasma when used as a suspension medium improves pigmentation due to its various growth factors.^[41]

Methods have also been devised to make the procedure simple including battery devices^[42] and welled plates.^[43,44] These techniques eliminate the need for sophisticated instruments and lab set up, with just as good outcomes. Also the need for incubator for warm trypsinization can be bypassed by taping the donor epidermal tissue in an Eppendorf tube to the axillary vault for 50 minutes.^[45] The Jodhpur technique is a modification in which there is no trypsinization step. It has been shown to have slightly better repigmentation compared to follicular unit transplantation.^[46] In order to retain the transplanted material on uneven contours, a putty material can be used as a scaffold.^[47] Advantages of NCES include coverage of large areas in single sitting, good cosmetic outcomes, and excellent color match [Figure 4].

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Figure 4:

Repigmentation after non-cultured epidermal cell suspension in a patch of vitiligo (a) at 2 months (b) and 6 months with almost complete repigmentation and excellent color match.

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Cultured epithelial grafts

This method produces a large epidermal sheet with the help of co-culture of keratinocytes and melanocytes.^[48]

Non-cultured outer root sheath hair follicle cell suspension (NCORSHFS) [Figure 5]

The outer root sheath, mid-follicle region and hair bulb matrix is a rich source for melanocytes and its precursors. It is done after follicular unit extraction or by plucking hair follicle, followed by follicular unit suspension.^[49,50] The trypsinization steps are similar to those of the NCES technique. There is a strong correlation between the number of melanocytes transferred and the repigmentation.^[51]

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Figure 5:

Procedure of non-cultured outer root sheath hair follicle cell suspension (a) hairs extracted from the occipital area using 1 mm disposable plastic punches; (b) hair follicles placed in a new tube of trypsin-EDTA after 30 minutes; (c) extracted hair follicles in Petri dish prior to trypsinisation; (d) after treating with trypsin thin keratinous hair shaft are left behind; (e) hair follicles in normal saline prior to transportation to laboratory (left) and cell pellet formed by centrifuging for 5 minutes at 1000 rpm (right).

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Combined epidermal and hair follicle suspension

Combined NCES and NCORSHFS has a better result combined than either alone. This is probably due to the higher levels of melanocyte growth factors and OCT4+ stem cells.^[52]

Dermabrasion

The most conventional method of performing this is to use a Manekshaw’s dermabrader [Figure 6]. The device is available in various sizes and is held like a pen and with a horizontally circular motion, the recipient site is prepared. It has the advantage of being cheap, and not requiring electricity. However, it requires a greater amount of effort and time to prepare the recipient site. Also, there is a higher rate of unevenness, and requires greater dexterity while treating margins and areas with pigment in between. It is easier to perform on surface which are flat and have a concave or convex surface such as the periorbital region. An underlying bony support makes it effortless, and it becomes arduous on surfaces like the genitalia and lips. The procedure can be made easier by applying a peel with 25% trichloroacetic acid prior to the dermabrasion.^[53]

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Figure 6:

Manekshaw’s dermabrader of different sizes.

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The effort can be offloaded on machine with the use of a motorized dermabrader. This consists of a device which has a rapidly rotating rough surface such as a diamond fraise, wire brush, or serrated wheel. The usual setting for a diamond fraise is to set the wheel rotating at 10,000 rotations per minute.

In both, the manual and the motorized dermabraders, the end point is pin point bleeding. This indicates that the abrasion process has achieved a depth of papillary dermis. Any deeper can result in scarring and any superficial can result in poor uptake.^[54]

Electrofulguration^[55,56]

This technique uses electrical current alternating at a frequency of 500–4000 Hz. It has a myriad of applications based on the output waveform, in electrofulguration in particular the current is damped and in the form of a sine wave. In the method of electrofulguration, there is no contact of the electrode with the skin and the current leaps from the electrode to the target. Although a multitude of electrode shapes are available, the classical one used in the unclassical indication of vitiligo surgery is the ball shaped one. This allows for a better delineation of the margins, and does not spill over into healthy tissue [Figure 7]. Its independence of friction allows it to be used over sites with no underlying bony structure, as well as on convex and concave surfaces. The drawbacks however include absence of the pin point bleeding leading to difficulty in depth control. Also, there is a chance of skip areas.^[57]

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Figure 7:

Dermabrasion with ball-tipped electrofulguration probe and frosting at the edges (a) complete frosting at the patch (b) and (c) after removal of the frost with saline soaked swab.

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Cryotherapy

Liquid nitrogen is the cryogen conventionally used to prepare the recipient sites, and the donor tissue is usually obtained from a suction blister graft. The procedure produces a cryoblister at recipient site after 24 hours if 3–6 freeze thaw cycles with a duration of 3–5 seconds each are used [Figure 8].^[58] However, the procedure is associated with complications like perilesional hyperpigmentation, hypertrophic scarring, and hypopigmentation.^[59] The hypopigmentation can be prevented by adding PUVA therapy concurrently.

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Figure 8:

A patch of vitiligo over dorsum of finger (a) at day 0 and cryoblister at day 1 (b).

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Suction blister

This method is versatile and can be used to prepare both the recipient area and the donor tissue. The technique is the same as described in donor tissue preparation. The serous discharge associated with this technique is thought to provide a better micro environment.^[60]

PUVA

The phototoxic potential of psoralens can be exploited to prepare the recipient area in a large site. It can be performed with the help of 0.075% 8-methoxypsoralen, applied topically 10 minutes prior to exposure to UVA radiation of 10 J/cm² per day for two consecutive days.^[61] This technique does not go beneath the reticular dermis and thus does not scar.^[62]

CO₂laser

Conventionally, the CO₂ laser is used for ablative resurfacing in a defocussed mode. Since long pulse has a risk of uncontrolled tissue damage and potential for scarring, the ultra-pulse mode and short-pulse mode can be used in vitiligo recipient site preparation. Coupled with scanning devices, it can provide uniformity in depth of ablation along with precision and greater speed. The main drawback with this method is the high cost.^[63] The parameters that can be used are 4.5 W, 0.2 sec pulse duration, 0.4 sec rest duration, 3-mm laser spot size with an attached scanning device.^[64]

Er-YAG laser

The higher affinity of this laser for water and lesser depth of penetration both make it suitable for resurfacing in vitiligo lesions. It can be applied on larger areas and provides the advantage of a blood-less field. Another advantage offered is the lack of need of anesthesia. The parameters that can be used are spot size 2 mm, 200–500 mJ with a fluence of 6.37–15.92 J/cm².^[65]