Laser-Tissue Interactions and Complications

1.    Introduction
Tattoos have been a part of costume, expression, and identification in various cultures for centuries. Although tattoos have become more popular in western culture, many people regret their tattoos in later years.  (Burris & Kim, 2007)

There are five types of tattoos: amateur, professional, cosmetic, medicinal, and traumatic. (Kuperman-Beade & Levine, 2001).   The type, color, and location of the tattoo, as well as the age and skin type of the patient, often dictates the choice of laser wavelength, fluence and spot-size setting, and the number of required treatments.  (Jow, Brown, & Goldberg, 2010)

Many different kinds of removal methods have been used throughout the centuries, such as chemical (trichloacetic acid), mechanical (dermabrasion), surgical excision and electrocautery. (Mohammad & Mahmood, 2009)
These destructive methods of removal, which wreaked havoc not only on the tattoo but more prominently on the skin containing that tattoo. (E. F. Bernstein, 2007)
Laser tattoo removal is the current treatment of choice, given its safety and efficacy.  It is important to be aware of the mechanisms of laser tattoo removal, as well as their potential short- and long-term effects. (Burris & Kim, 2007)

(Relatively few advances have been made since that time, although there are new promising discoveries on the horizon. (E.F Bernstein, 2006)

2.    The lasers most commonly used for tattoo removal have been identified and discussed with regards to their properties of wavelength, chromophore, pulse duration and TRT relevance.
New laser technology has been discussed briefly.
The 4 most common lasers.
Three types of lasers are currently commercially available for tattoo removal: the Q-switched ruby laser (694 nm), the Q-switched alexandrite laser (755 nm) and the Q-switched Nd:YAG laser (532 nm and 1064 nm). Multiple parameters such as tattoo type, color, location, and patient skin type dictate which laser is optimal in each patient. (Jow et al., 2010)
Q-switched (QS) lasers are widely considered the gold standard for tattoo removal, with excellent clinical results, impressive predictability, and a good safety profile.  (Barua, 2015)
These include the quality-switched Neodymium : Yttrium Aluminium Garnet laser (QS Nd:YAG, 532 nm and 1064 nm), quality-switched Ruby (QSRL, 694 nm) laser and the quality-switched Alexandrite (QSAlex, 755 nm) laser.5  (Varma & Lee, 2002)
a.    The Q-switched ruby laser (QSRL) — the QSRL emits light at a wavelength of 694 nm and has a pulse duration of 28-40 ns. ?
b.    The Q-switched alexandrite laser (QSAL) — the QSAL has a near infrared wavelength of 755 nm, pulse duration of 50-100 ns, ?spot size of 2-4 mm, and a repetition rate up to 10 Hz. ?
c.    The Q-switched neodymium-doped yttrium aluminum garnet (QS Nd:YAG) laser —emits infrared light ?at 1,064 nm and has a pulse duration of 5-10 ns, spot size of 1.5-8 mm, and a repetition rate up to 10 Hz. The frequency can be doubled and the wavelength can be halved (532 nm) by passing the laser beam through a potassium titanyl phosphate (KTP) crystal. ?(Barua, 2015)

The QS lasers work by impaction and dissolution of the tattoo pigments. Mechanical fragmentation of the tattoo pigments encased in intracellular lamellated organelles followed by their phagocytosis by macrophages is thought to be the major event in the clearance of pigments by QS lasers. A few novel techniques have been tried in recent times to hasten the clearance of tattoo pigments.  (Barua, 2015)
Amateur tattoos require less treatment sessions than professional multicolored tattoos.  Factors to consider when evaluating tattoos for removal are: location, age and the skin type of the patient. (Kuperman-Beade & Levine, 2001)
A tattoo is made of particles of pigment injected into the skin. Although the body attempts to remove them, the particles of tattoo are too large to be removed and the body responds by encapsulating the whole tattoo in a wall of collagen that traps it within the skin permanently.? (Mohammad & Mahmood, 2009)
Tattoo ink particles are disrupted and broken up by the photomechanical and photothermal effects of laser energy, and it has been theorized that the optimal pulse width is within the picosecond range, allowing for a safer and more efficient procedure [8]. The recent addition of the alexandrite picosecond laser has shown great promise in rapid effective removal of blue and green inks. The exact mechanism of yellow pigment destruction remains unclear as no laser wavelength is available that directly targets the yellow chromophore, suggesting yellow pigment maybe more susceptible to the photomechanical effect  (Alabdulrazzaq, Brauer, Bae, & Geronemus, 2015)
Tattoo inks are composed of pigments that are suspended in a carrier solution. The tattoo pigments range from inorganic materials to azo dyes, with variable absorption spectra.[2,3] They are primarily metal salts but can also be an assortment of plastics and vegetable dyes [ Table 1]. The pigment provides the color of the tattoo. The carrier may be a single substance or a mixture. The purpose of the carrier is to keep the pigment evenly distributed in a fluid matrix, to inhibit the growth of pathogens, to prevent clumping of the pigment, and to aid in application to the skin. The most common ingredients in the carrier are ethyl alcohol, purified water, witch hazel, ListerineTM, propylene glycol, and glycerol. (Barua, 2015)
Q-switching, or quality switching, of a laser is a mechanism used to control the light output by concentrating all the energy into intense bursts or series of pulses by modulating the intracavity losses, the so-called Q factor of the laser resonator.   The technique is mainly applied for the generation of nanosecond pulses of high energy and peak power with solid-state bulk lasers. Laser devices that incorporate Q-switching are able to achieve selective photothermolysis due to their high energy and short-pulse duration. This can be applied in the setting of removal of the tattoo pigment to arrive at the desired clinical results without much damage to the surrounding tissues, and with relatively faster and uncomplicated healing time.[6]
The key requirement to laser tattoo removal is that the light must reach and be absorbed by the tattoo.  (Bernstein., 2006)
professional tattoos involve a wider variety of pigments that are placed deeply and densely into the dermis.[1,2,3] This creates challenges in selecting the appropriate laser and achieving complete clearance. (Sardana, Ranjan, & Ghunawat, 2015)
Professional tattoos are notorious for their wide range of undocumented chemical compositions and will continue to pose therapeutic challenges, (Sardana et al., 2015)
Q switching is a means of producing a very short laser pulse in the nanosecond domain.  (E.F Bernstein, 2006)
Anderson and Parrish,47 in their seminal article describing the concept of selective photothermolysis, which is the ability to remove target tissues in skin without hurting the surrounding unaffected skin, state that small targets are best treated with pulses in the nanosecond range. (E.F Bernstein, 2006)
Q-switched lasers have become, and remain, the mainstay of modern tattoo removal. There are three types of Q-switched lasers: the ruby, alexandrite, and neodymium:yttrium-aluminum- garnet (Nd:YAG) lasers. (E.F Bernstein, 2006)
Typically, ruby lasers have been very effective at removing black and dark blue tattoo pigments (Fig. 5). In addition, amateur, traumatic, and medically placed tattoos used as markers for administering radiation therapy respond quite well to the Q-switched ruby laser.  (E.F Bernstein, 2006)
In general, there are five categories of tattoos: professional, amateur, cosmetic, medicinal, and traumatic.
It is important to note that there are considerable differences between the three available laser wave- lengths used for tattoo removal.The Q-switched ruby and alexandrite lasers are optimal for removing black, blue and green pigments; the Q-switched 532 nm Nd:YAG laser can be used to remove red pigments; and the 1064 nm Nd:YAG laser is ideally used for removal of black and blue pigments (Jow et al., 2010)
New laser technology discussed briefly
Combination laser treatment Non-ablative or ablative fractional resurfacing has been reported to be effective for tattoo removal, either when combined with QS ruby laser treatment or as monotherapy.   (Ho & Goh, 2015)
Multi-pass treatments e R20 method of tattoo removal, where accelerated lightening can be achieved by using four laser passes in one treatment session, with an interval of 20 min between the passes.[38] The 20 minutes waiting time allows for the post-laser immediate whitening to resolve completely before a second pass is given. (Ho & Goh, 2015)
Monotherapy with QSL is often effective for tattoo removal but combining QS laser with an ablative fractional laser or nonablative fractional laser may yield faster clearing, minimize number of sessions, and reduces side effects. The combination can be in any order; FL followed by QSL helps reduces blister formation.  (Shah, 2015)

Pulse diameter (Picosecond lasers) Most tattoo pigments have a particle size of 30-300 nm, corresponding to a thermal relaxation time of less than 10 nanoseconds.[18] Thus an ideal laser should have a pulse duration in nanoseconds, which is the logic of using QS lasers (10-9 s). Newer laser technologies shorten that pulse time to picoseconds (10-12 s), promising more effective results in tattoo removal. (Sardana et al., 2015)
But pulsed lasers like Er:YAG and the ultrapulsed CO2 lasers can be used to precisely remove epidermal layers. [29,30] This was studied using a combination of ultrapulse CO2 laser followed by QS Nd:YAG,[29] in a split lesion design which lead to a significant reduction in the number of sessions with negligible side effects [Figure 3 ]. This has been further modified using the Er:YAG followed by the QS Nd:YAG with better results and has been christened the Rapid Tattoo Removal technique (RTR)  (Sardana et al., 2015)
Picosecond lasers
These lasers have been developed as the need for lasers with shorter pulse durations than the above Q-switched lasers, to decrease the number of treatments necessary to remove tattoos and optimize treatment (Choudhary, Leiva, & Nouri, 2010)
QS lasers emit short, high-intensity pulses that cause thermomechanical destruction via photoacoustic waves, leading to the fragmentation of tattoo pigments encased in intracellular lamellated organelles. The subsequent phagocytosis of fragmented ink particles results in gradual fading and clearance of the tattoo pigments. (Barua, 2015)
The concept of selective photo- thermolysis was explained by Anderson and Parrish as the ability to remove target tissues in skin without causing any damage to the surrounding tissues, by a given wavelength of laser light  (Choudhary et al., 2010)
The theory of selective photothermolysis plays an essential role in the laser tattoo removal process as the duration of light exposure must be less than the thermal relaxation time. Current Q-switched lasers are able to yield extremely short laser pulses with durations in the nanosecond range and there- fore permit the specific heat confinement needed for photoacoustic destruction of these pigments’ chromophores and particles.  (Jow et al., 2010)
The concept of selective photothermolysis revolutionized the treatment of tattoos by preferentially targeting the tattoo pigment with specific wavelengths and pulse durations of laser light that the tattoo ink particles selectively absorb while adjacent structures are left essentially unharmed.47 Tattoo ink particles are small and therefore require Q-switched (QS) laser systems with brief (nanosecond) pulse durations. The high energy delivered over an ultrashort time period results in shattering of the ink particles, which are then engulfed by tissue macrophages and cleared by the lymphatic system or through trans epidermal elimination. (Ortiz & Alster, 2011)
Newer techniques for tattoo removal involve combinations of QS pigment-specific (red and infrared) lasers with ablative fractional laser resurfacing, which have been reported to enhance the rate of pigment clearance and decrease risk of vesiculation.54?Other novel technologies include the picosecond laser, which has been shown to be better in tattoo pigment clearance than the nanosecond lasers in Yorkshire pigs (Ortiz & Alster, 2011)
Q-switched lasers with light having wavelength in the visible and near-IR region …… Because of the inhomogeneous distribution of the pig- ment in the skin, the strength of the laser-pulse tissue interaction varies even within a single tattoo (Cencic & Gregorcic, 2012)
There is a controversy in the literature surrounding the mechanism of tattoo pigment reduction in tissue. The two major mechanisms, which have been proposed for the fragmentation of tattoo ink granules, are thermal and acoustic. Though majority of studies have focused on fragmentation through thermal mechanisms,[4] some have suggested that the acoustic mechanism predominates in short pulsed laser therapy.[5,6] In contrast, Welch et al. [7] suggested that the laser-induced damage may be caused by a combination of thermal and acoustic effects. Accordingly, a wide range of predicted optimal parameters for laser treatment have been suggested, which make the settings and parameters subject to variation.
The ultimate goal is to minimise sessions and maximise results. Total clearance of a tattoo is not often seen and one study reported that only three of 238 paying patients achieved this goal.[8] Thus, a constant endeavour is to optimise laser parameter selection, increase the efficacy of each treatment session, and minimise the total number of treatment sessions required.[1,2,8] (Sardana et al., 2015)
The number of treatment sessions also depends on pigment colour, composition, density, depth, age of the tattoo, body location and the amount of tattoo ink present. (Sardana et al., 2015)
More recently placed tattoos with deeply located pigment on a distal site are harder to remove due to the reduced lymphatic distribution which helps in removing residual ink particles (Sardana et al., 2015)

selective photothermolysis. This implies that the laser causes targeted destruction of the tattoo pigments by means of selectively absorbed wave- length and a pulse duration shorter than the thermal relaxation time (the time a structure needs to cool down to half the temperature to which it was heated). This would result in only minimal damage to the epidermis, dermis, and skin appendages, while selectively destroying the target pigment, which acts as the chromophore for the laser  The tattoo ink is an exogenous chromophore.
Q-switching is a technique that produces nanosecond laser pulses by suddenly releasing all of the excited-state energy from a laser medium. A whitening reaction occurs upon exposure to this laser. (Choudhary et al., 2010)
Anderson and Parrish, in their landmark papers on skin optics,[7,8,9] propounded the theory of selective photothermolysis. This theory postulates that light of a wavelength that is absorbed by a target chromophore will selectively damage or destroy that chromophore if the fluence is sufficiently high and the pulse duration is less than or equal to the thermal relaxation time (TRT) of that chromophore. It follows, therefore, that if the laser pulse duration is less than the TRT of the target chromophore, heat diffusion does not take place and the damage is selectively confined to the target without any collateral injury to the surrounding tissues.
QS lasers work on the principle of selective photothermolysis and also produce an additional photoacoustic effect, producing shock waves that cause explosion of the target.[8,10,11] Very high energy to the tune of 300 MW is delivered in a very short period of time (5- 100 ns), which leads to rapid thermal expansion. This produces shock waves that rupture the targeted ink particles.[12,13] Phagocytosis of the pigment by macrophages is the primary method of elimination. The ruptured fragments are directed by tissue macrophages either to the lymphatic channels or to the regional lymph nodes. Some fragments may be transepidermally eliminated as the posttreatment crust is sloughed off.[5,14]  (Barua, 2015)
the skin contains three major chromophores—hemoglobin, melanin, and water—lasers that are absorbed strongly by these wave- lengths would have to compete with these chromophores for absorption. Thus, the competing chromophores of melanin, hemoglobin, or water would take up some of the laser energy not allowing it to reach the tattoo granules. Currently available Q-switched lasers are ideal for tattoo removal in the sense that they are absorbed poorly by competing chromophores and penetrate deeply. (E. F. Bernstein, 2007)

3.    The mechanism of action of laser tattoo removal has been discussed in detail by considering laser-tissue interactions. – considering laser-tissue interaction.  Systemic interaction – lymphatics discussed.
Photothermolysis describes the ability to remove targets from within skin or other tissues without affecting the surrounding, uninvolved skin. These targets can be virtually anything that takes up laser energy such as blood vessels, melanin pigment, or tattoo particles. Anderson and Parish state that small particles such as tattoo granules should be treated with pulses in the nanosecond domain. (E. F. Bernstein, 2007)

To be selective, the pulse duration of the laser should match the TRT of the target. The estimated TRT of the epidermis is 1-10 ms and the TRT of the tattoo ink particles is 0.1-10 ns, although some newer estimates are in the range 10-100 ps.[5] The size of the tattoo ink particles is about 10-100 nm and is generally placed at a depth of 1.1-2.9 mm. Laser-tissue interaction produces intercellular steam and vacuole formation within the target pigment that cause a scattering of visible light, leading to immediate whitening. An audible popping sound is heard during the laser procedure due to the photoacoustic effect. (Barua, 2015)
There are several variables that influence tattoo removal using the QS lasers. Smoking, the presence of colors other than black and red, a tattoo larger than 30 cm2, a tattoo located on the feet or on the legs, one that is older than 36 months, one with a high color density, treatment intervals of 8 weeks or less, and the development of darkening phenomenon are associated with reduced clinical response rates.[17] (Barua, 2015)
The Kirby-Desai Scale is a useful index to correlate with the number of treatment sessions required for satisfactory tattoo removal. It is based on six tattoo criteria – skin type, location, color, amount of ink, scarring, and layering.[18]   (Barua, 2015)  (Kirby, Desai, Desai, Kartono, & Patel, 2009)
Tattoo-removing lasers must be absorbed by the tattoo granules to effect removal. Because today’s tattoo pigments come in a myriad of colors, multiple wavelengths of light may be required to remove a single tattoo. In addition to variations in color, tattoos may become resistant to certain wavelengths of light in a manner similar to bacteria becoming resistant to antibiotics. Thus, multiple wavelengths of light may be required to remove even the simplest of colors to treat, such as black, with minimal or no scarring.  (E. F. Bernstein, 2007)

Understand the variables involved in tattoo removal which are depicted in Figure 1 and Table 1. Three broad aspects are involved, the laser(s) used, the skin phenotype and tattoo dependant factors, which includes the type, depth and size of tattoo [Figure 1]. A rarely appreciated aspect of tattoo removal is the role of the host immune response, which ultimately phagocytoses the tattoo particles and drains them away via the lymphatics.  Thus it is the inflammation consequent to the laser therapy and the concomitant stimulation of the host response that ultimately results in removal of tattoo ink via the lymphatics.  (Sardana et al., 2015)
Tattoo pigments, which consist of insoluble, sub-micrometers – sized particles that are phagocytosed by dermal cells, react almost the same way as melanosomes. Tattoo particles, sometimes grouped in granules and packed into vacuoles from 0.1 to 10 microns in diameter, are endocytosed by fi- broblasts as well as macrophages in the dermis and sometimes in the subcutis.  (Adatto, 2004)
The absorbtion of light pulses by the tattoo pigments is the first and most important step. If there is no absorbtion, there is no reaction. Immediately after impact, the epidermis looks white which corresponds to gas forma- tion. This whitish colouration disappears spontaneously within minutes. The tattoos pigments absorb the short laser pulses, 10–9 sec, so called Q-switched (Adatto, 2004)
In- side the pigments, this light is converted into heat with- in nanoseconds, producing an increase in temperature above 1000 °C (photothermal effect). This rapid ther- mal expansion produces shock waves and a potential localized cavitation, so called photoacoustic shock which leads to a particle fragmentation and selective death of pigment containing cells. There is also at the same time a breaking in the chemical bonds inside the pigment (photochemical effect). The inflammatory reponse that follows this process probably engulfs the cells debris as well as the fragmented tattoo pigments. This process of inflammation and phagocytosis might reduce the overall amount of tattoo pigment into the dermis. These particles, as well as their decomposition products, are usually found in regional lymph nodes. Some of the fragmented particles stay in place within the dermis, but as they are redistributed by the laser photoacoustic shock, their dermal scattering coefficient changes and they look less visible to the naked eye as they are located deep in the dermis. Finally, the only part of the pigment which is really eliminated from the body is a very superficial one as it is eliminated by desquamation of epidermis during its repair (19, 20). This phenomenon is called transepidermal elimination. (Adatto, 2004)
Generally, tattoo pigments are comprised of inorganic and/or organic compounds, such as chromium, mercury, iron, copper, carbon, and polycyclic compounds. The diversified composition of tattoo pigments results in competing chromophores, usually with different absorption spectra
(Jow et al., 2010)
As the tattoo ages, the tattoo’s pigment granules become engulfed by resident dermal fibro- blasts and macrophages and can be found within their lysosomes. Ultimately, laser tattoo removal is accomplished by photoacoustic destruction of the tattoo particles.This leads to the formation of smaller fragments that can then be more easily removed via the vascular or lymphatic systems, re-phagocytosis by mononuclear cells, or elimination through the epidermis (Jow et al., 2010)
Q-switched lasers have now become the standard for removal of tattoos. However complications can occur.  On delivery of the laser in the skin, the energy that is absorbed by the pigment is converted to heat, which is the photothermal effect. There is breakage of chemical bonds inside the pigment, which is the photochemical effects. There is a mechanical destruction of the pigments due to photoacoustic effects. Small pigment particles, unknown decomposition products and newly generated chemical compounds are then removed from the skin via blood vessels or the lymphatic system (Khunger, Molpariya, & Khunger, 2015)

There are also structural changes noted in the pigment particles. Depending on the dosage, temporary whitening may occur during the treatment. Whitening is caused by rapid local heating of the pigment leading to gas or plasma formation and subsequent dermal and epidermal vacuolization. The whitening reaction appears immediately with the use of the laser and is replaced by a scab in 2–5 days. A test spot with the laser provides an opportunity to test the suitability of a particular laser for a skin phototype or tattoo response to laser treatment. The small test area can then be reevaluated in 1 month. Post-procedure patients must be instructed to apply a petrolatum-based emollient on the treated area until the scab falls off (Choudhary et al., 2010)
Temporary local side effects like erythema, burning, edema, crusting, and pain should be considered as a normal skin reaction following laser treatment. s laser treatment creates a superficial wound, especially immunosuppressed patients are at risk of developing local skin infections. A thorough medical history is mandatory before laser treatment to identify possible risk factors for such side effects.(Klein, Rittmann, & Hiller, 2013)

4.    One major complication specific to laser tattoo removal has been identified and discussed on a cellular level in great detail.
COMPLICATION
However side- effects and complications can result from laser attempts at removal such as scarring, infection, bleeding, hypopigmentation, hyperpigmentation, partial lightening and tattoo ink darkening. (Varma & Lee, 2002)

Side effects do occur, many of which are thermally mediated. The most frequently occurring temporary side effects of laser tattoo removal include pain, erythema, crusting, pinpoint bleeding, blistering, swelling, infection, and pigmentary disorders. Permanent side effects include mainly scarring, hypo- or hyperpigmentation, and color change of tattoo pigment(Klein et al., 2013)
Risk factors for the development of side effects are darker skin type, tanning, intake of photosensitizing agents, and a predisposition to develop hypertrophic scars or keloids. Furthermore, applying the wrong wavelength or non-appropriate pulse durations might lead to severe side effects (Klein et al., 2013)
Side effects and limitations of laser tattoo removal include the need for multiple treatment sessions, risks for hypo- and hyperpigmentation, post-treatment bleeding, blistering, and infection, and textural changes. Hypopigmentation most commonly occurs with the Q-switched ruby laser, whereas hyperpig- mentation is more commonly seen with all Q-switched lasers when darker skin types are treated (Jow et al., 2010)
As the treatments can be painful, time-consuming, and costly, many patients become discouraged over the course of their treatment many truncate the number of their sessions, resulting in inadequate results. Thus, it is important to evaluate the issues affecting patient compliance and its overall impact on the success rates of laser tattoo removal
(Jow et al., 2010)
The complications of laser tattoo removal can be divided into immediate and delayed (Khunger et al., 2015)
Immediate include pain, blisters [Figure 4], crusting and pinpoint haemorrhage [Figure 5]. These are more common in darker skins, using a high fluence.  (Khunger et al., 2015)
The most common delayed complication is pigmentary changes, either hypopigmentation [Figure 6] or hyperpigmentation. These occur 4-6 weeks after laser treatment and most of them are transient. However, longer- lasting pigmentary alterations can occur, especially in darker or tanned skin.  (Khunger et al., 2015)
Hypopigmentation. In addition to the interaction with tat- too pigments, quality-switched laser devices destroy melanosomes in the skin, which are similar in size and cellular location as tattoo pigments. The greater melanin absorption seen with shorter wavelengths increases the risk of hypopigmentation. This occurs in about 5–10% of the cases11,12 and is mostly transient, but can be permanent;13 it is also more closely related to the main effect – pigment removal – than to an actual side effect and thus not limited to false usage of the laser.  (Karsai, Krieger, & Raulin, 2009)

There has been a exponential increase in decorative tattooing as a body art in teenagers and young adults. Unfortunately there are no legislations to promote safe tattooing, hence complications are quite common. Superficial and deep local infections, systemic infections, allergic reactions, photodermatitis, granulomatous reactions and lichenoid reactions may occur. Skin diseases localised on the tattooed area, such as eczema, psoriasis, lichen planus, and morphea can be occasionally seen. (Khunger et al., 2015)
Acute complications include pain, blistering, crusting and pinpoint hemorrhage. Among the delayed complications pigmentary changes, hypopigmentation and hyperpigmentation, paradoxical darkening of cosmetic tattoos and allergic reactions can be seen. Another common complication is the presence of residual pigmentation or ghost images. Scarring and textural changes are potential irreversible complications (Khunger et al., 2015)
These occur mainly due to the unsterile pigments that are implanted and unsterile conditions in which they are carried out. Different reactions have different times of onset as few of them appear immediately after the procedure and some may take days to weeks to years to appear (Khunger et al., 2015)
The most commonly reported reactions were tenderness and itching associated with allergic reactions and bumps secondary to granulomatous reactions.2  (Ortiz & Alster, 2011)
The lichenoid pattern is the most common and is thought to represent a delayed hypersensitivity reaction (Ortiz & Alster, 2011)

Cutaneous lymphoid hyperplasia (CLH)
CLH or pseudolymphoma comprises of a heterogeneous group of benign T- or B-cell lymphoproliferative reactions that are either idiopathic or associated with stimuli such as drugs or contact dermatitis. Approximately 20 cases of tattoo-induced CLH have been reported to date where they have occurred as asymptomatic or itchy, single or multiple, nodules or swellings [8–12]. It is mostly related to red color, but associations with blue and green are also known. This reaction can greatly resemble a lichenoid or granulo- matous reaction [7]. The most recent report on CLH in tattoos was a case series of seven patients who developed CLH with tattoos. Their skin biopsies and contact test were performed and suggested a combined T- and B- cell response [13]. To date, only one case of lymphoma developing in CLH in a tattoo has been reported (Choudhary et al., 2010)

One of the most common mistakes novice laser surgeons make is increasing the laser fluence in refractory tattoos by shrinking the spot size. This places more of the administered energy superficially in the skin, resulting in a greater chance of scarring and side effects  (Bernstein., 2006)
This is as the laser merely works by disruption of the tattoo and it is the host tissue response that effects the phagocytosis and expulsion of the tattoo from the skin via the lymphatics.[3,4,26] Patients suffering from short- and long-term immunosuppression (i.e., via chemotherapy, drug-induced, or a medical condition) may experience poor healing, which can further lead to ink retention following laser treatments.[41] This is specially relevant in patients on oral steroids, azathioprine and cyclophosphamide, often prescribed by dermatologists.
Individuals presenting with underlying immunosuppression should be referred to the appropriate specialist for comprehensive care. Once the condition has stabilised or resolved, they should be considered appropriate candidates for laser tattoo removal treatment (Sardana et al., 2015)

Dyspigmentation and textural changes
As melanin is the main competing pigment when treating tattoos with Q-switched lasers, increased melanin absorption with shorter wavelengths has resulted in hypopigmentation [50, 53]. This may be transient (seen with 510- and 532-nm lasers) or long-term (seen with QSRL). Gundogan et al. [54] treated hypopigmented areas that had remained unchanged for over 4 years after tattoo removal with the Q-switched Nd: YAG laser, using the 308-nm xenon-chloride excimer laser. It induced a significant repigmentation in 40 sessions over 14 months. The excimer laser has the potential to influence the reduced activity of the melanocytes, as was demonstrated with electron microscopy.
Hyperpigmentation is another concern more in the darker-skinned individuals, so they can be better treated with the Nd:YAG laser, the longer wavelength of which better spares the epidermis. If QSRL or Q-switched alexandrite lasers must be used, then it should be compensated by lower fluences. Also, dark-skinned and tanned individuals should be treated with bleaching agents before initiating laser treatment. Additionally, in patients prone to pigmentary and textural changes, longer treatment intervals may be helpful. Patients should avoid sun- exposure. Treatment may consist of hydroquinone and regular use of sun protection. Fractional photothermolysis may be considered  (Choudhary et al., 2010)

5.    A discussion indicating how complications and side effects of laser tattoo removal in general may be minimized in clinical practice.
With the increasing incidence of tattooing as a fashion trend in society, clinicians should be able to recognise and treat those complications at the earliest and also appropriately counsel their patients on risks of tattoo placement. Thorough clinical history and examination are essential to make a diagnosis. To confirm the diagnosis, skin biopsy is mandatory, especially with a papulonodular growth within the tattoo pigment, since neoplastic conditions are not immediately recognised with clinical examination only.  (Khunger et al., 2015)
The laser should be chosen according to the colour of the tattoo pigment and the patient’s skin type. Generally Q- switched 1064nm Nd:YAG laser is safer in darker skin types 5-6. The spot size, the fluence and the pulse duration are important and should be carefully selected. (Khunger et al., 2015)
Risk factors for the development of side effects are darker skin type, tanning, intake of photosensitizing agents, and a predisposition to develop hypertrophic scars or keloids. Furthermore, applying the wrong wavelength or non-appropriate pulse durations might lead to severe side effects (Klein et al., 2013)
Sun avoidance is an important measure to prevent side effects when performing laser therapy as the epidermal mel- anin competes for absorption of laser light in skin. If a patient is suntanned, treatment should be delayed or a Q-switched Nd:YAG laser should preferably be used due to its longer wavelength. Hypopigmentation is a frequently described side effect of laser therapy. Fitzpatrick et al. [15] described hypopigmentation in 50 % of patients after Q-switched alexandrite laser tattoo removal, which is in accordance with our results. These pigmentary changes might be transient(Klein et al., 2013)

6.    CONCLUSION
Laser treatment requires multiple painful sessions that are expensive and sometimes incompletely successful. With an increase in the number of ink colors, tattoo removal is becoming increasingly difficult.  (Ortiz & Alster, 2011)
Although the Q-switched lasers are capable of removing tattoos without harming the skin, removal often takes numerous treatments and still can be incomplete, especially when attempting to remove multicolored tattoos. Developments leading to removable tattoo inks, feedback systems to detect the absorbance characteristics of tattoo inks, dermal clearing agents, and perhaps even shorter pulse-duration lasers should result in improvements in tattoo removal in the near future. (E. F. Bernstein, 2007)

There are still many improvements that can be made in the field of laser tattoo removal to increase the efficacy of these treatments so that results can be obtained faster and prove more tolerable for the patients. Such advances include new research in pico- and femto-second lasers as well as the development of laser-susceptible tattoo inks.
(Jow et al., 2010)

QS lasers, based on the principle of selective photothermolysis, provide for techniques of tattoo removal that achieve selective removal of each tattoo pigment with minimal risk of scarring and/or pigmentary alteration. Since many wavelengths are needed to treat multicolored tattoos, a single laser system cannot be used alone to remove all the available inks and its combinations. Several studies[24,25] have concluded that picosecond pulses are more efficient than nanosecond pulses at tattoo particle fragmentation. Current research is, therefore, focusing on newer picosecond lasers, which may be more successful than the QS lasers in effective and rapid clearance of the new vibrant tattoo inks. (Barua, 2015)

Stop and think before you ink holds very much true in the present scenario. (Khunger et al., 2015)

It has been rightly sung by Jimmy Buffett, an American singer that a tattoo is a permanent reminder of a temporary feeling. (Khunger et al., 2015)

Bibliography

Adatto, M. A. (2004). Laser Tattoo Removal- Benefits and Caveats. Medical Laser Application, 19, 175-185.
Alabdulrazzaq, H., Brauer, J. A., Bae, Y. S., & Geronemus, R. G. (2015). Clearance of yellow tattoo ink with a novel 532-nm picosecond laser. Lasers Surg Med, 47(4), 285-288. doi:10.1002/lsm.22354
Barua, S. (2015). Laser-Tissue Interaction in Tattoo Removal by Q-Switched Lasers. Journal of Cutaneous and Aesthetic Surgery, Volume 8(1), 5-8. doi:10.4103/0974-2077.155063
Bernstein, E. F. (2006). Laser treatment of tattoos. Clinics in Dermatology, 24, 43-55. doi:10.1016/j.clindermatol.2005.10.025
Bernstein, E. F. (2007). Laser Tattoo Removal. Seminars in Plastic Surg, 21(3), 175-192. doi:10.1055/s-2007-991186
Bernstein., E. F. (2006). Laser treatment of tattoos. Clinics in Dermatology, 24, 43-55. doi:10.1016/j.clindermatol.2005.10.025
Burris, K., & Kim, K. (2007). Tattoo removal. Clinics in Dermatology, 25, 388-392. doi:10.1016/j.clindermatol.2007.05.011
Cencic, B., & Gregorcic, P. M. i., J. Jezers?ek, M. (2012). Laser tattoo removal as an ablation process monitored by acoustical and optical methods. Applied Physics A Material Science & Processing, 112, 65-69. doi:10.1007/s00339-012-7203-0
Choudhary, S. E., M.L., Leiva, A., & Nouri, K. (2010). Lasers for tattoo removal- a review. Lasers in Medical Science, 25, 619-627. doi:10.1007/s10103-010-0800-2
Ho, S. G., & Goh, C. L. (2015). Laser tattoo removal: a clinical update. J Cutan Aesthet Surg, 8(1), 9-15. doi:10.4103/0974-2077.155066
Jow, T., Brown, A., & Goldberg, D. J. (2010). Patient compliance as a major determinant of laser tattoo removal success rates: A 10-year retrospective study. Journal of Cosmetic and Laser Therapy, 12, 166-169. doi:10.3109/14764172.2010.503787
Karsai, S., Krieger, G., & Raulin, C. (2009). Tattoo removal by non-professionals – medical and forensic considerations. JEADV Journal compilation ª 2009 European Academy of Dermatology and Venereology, 24, 756-762. doi:10.1111/j.1468-3083.2009.03535.x
Khunger, N., Molpariya, A., & Khunger, A. (2015). Complications of Tattoos and Tattoo Removal: Stop and Think Before you ink. J Cutan Aesthet Surg, 8(1), 30-36. doi:10.4103/0974-2077.155072
Kirby, W., Desai, A., Desai, T., Kartono, F., & Patel, G. (2009). The Kirby-Desai Scale- A Proposed Scale to Assess Tattoo-removal Treatments. The Journal of Clinical & Aesthetic Dermatology, 2(3), 32-37.
Klein, A., Rittmann, I., & Hiller, K.-A. L., M. Ba¨umler, W. (2013). An Internet-based survey on characteristics of laser tattoo removal and associated side effects. Lasers Med Sci. doi:10.1007/s10103-013-1395-1
Kuperman-Beade, M., & Levine, V. J. A., R. (2001). Laser Removal of Tattoos. American Journal Of Clinical Dermatology.
Mohammad, F. A., & Mahmood, A. S. (2009). Removal of Tattoo By 1064 and 532nm Q-switched Nd- YAG laser. Iraqi Journal of Medical Sciences, 7(3), 66-81.
Ortiz, E., & Alster, T. S. (2011). Rising Concern over Cosmetic Tattoos. American Society for Dermatologic Surgery, Inc., 38(3), 424-429. doi:10.1111/j.1524-4725.2011.02202.x
Sardana, K., Ranjan, R., & Ghunawat, S. (2015). Optimising laser tattoo removal. J Cutan Aesthet Surg, 8(1), 16-24. doi:10.4103/0974-2077.155068
Shah, S. D. A., S.J. (2015). Newer Trends in Laser Tattoo Removal. Journal Cutaneous Aesthetic Surgery, 8(1), 25-29. doi:10.4103/0974-2077.155070
Varma, S. S., N.A., & Lee, K. K. (2002). Tattoo ink darkening of a yellow tattoo after Q-switched laser treatment. Clinical & Experimental Dermatology(27), 461-463.

Laser-Tissue Interactions and Complications

1.    Introduction
Tattoos have been a part of costume, expression, and identification in various cultures for centuries. Although tattoos have become more popular in western culture, many people regret their tattoos in later years.  (Burris & Kim, 2007)

There are five types of tattoos: amateur, professional, cosmetic, medicinal, and traumatic. (Kuperman-Beade & Levine, 2001).   The type, color, and location of the tattoo, as well as the age and skin type of the patient, often dictates the choice of laser wavelength, fluence and spot-size setting, and the number of required treatments.  (Jow, Brown, & Goldberg, 2010)

Many different kinds of removal methods have been used throughout the centuries, such as chemical (trichloacetic acid), mechanical (dermabrasion), surgical excision and electrocautery. (Mohammad & Mahmood, 2009)
These destructive methods of removal, which wreaked havoc not only on the tattoo but more prominently on the skin containing that tattoo. (E. F. Bernstein, 2007)
Laser tattoo removal is the current treatment of choice, given its safety and efficacy.  It is important to be aware of the mechanisms of laser tattoo removal, as well as their potential short- and long-term effects. (Burris & Kim, 2007)

(Relatively few advances have been made since that time, although there are new promising discoveries on the horizon. (E.F Bernstein, 2006)

2.    The lasers most commonly used for tattoo removal have been identified and discussed with regards to their properties of wavelength, chromophore, pulse duration and TRT relevance.
New laser technology has been discussed briefly.
The 4 most common lasers.
Three types of lasers are currently commercially available for tattoo removal: the Q-switched ruby laser (694 nm), the Q-switched alexandrite laser (755 nm) and the Q-switched Nd:YAG laser (532 nm and 1064 nm). Multiple parameters such as tattoo type, color, location, and patient skin type dictate which laser is optimal in each patient. (Jow et al., 2010)
Q-switched (QS) lasers are widely considered the gold standard for tattoo removal, with excellent clinical results, impressive predictability, and a good safety profile.  (Barua, 2015)
These include the quality-switched Neodymium : Yttrium Aluminium Garnet laser (QS Nd:YAG, 532 nm and 1064 nm), quality-switched Ruby (QSRL, 694 nm) laser and the quality-switched Alexandrite (QSAlex, 755 nm) laser.5  (Varma & Lee, 2002)
a.    The Q-switched ruby laser (QSRL) — the QSRL emits light at a wavelength of 694 nm and has a pulse duration of 28-40 ns. ?
b.    The Q-switched alexandrite laser (QSAL) — the QSAL has a near infrared wavelength of 755 nm, pulse duration of 50-100 ns, ?spot size of 2-4 mm, and a repetition rate up to 10 Hz. ?
c.    The Q-switched neodymium-doped yttrium aluminum garnet (QS Nd:YAG) laser —emits infrared light ?at 1,064 nm and has a pulse duration of 5-10 ns, spot size of 1.5-8 mm, and a repetition rate up to 10 Hz. The frequency can be doubled and the wavelength can be halved (532 nm) by passing the laser beam through a potassium titanyl phosphate (KTP) crystal. ?(Barua, 2015)

The QS lasers work by impaction and dissolution of the tattoo pigments. Mechanical fragmentation of the tattoo pigments encased in intracellular lamellated organelles followed by their phagocytosis by macrophages is thought to be the major event in the clearance of pigments by QS lasers. A few novel techniques have been tried in recent times to hasten the clearance of tattoo pigments.  (Barua, 2015)
Amateur tattoos require less treatment sessions than professional multicolored tattoos.  Factors to consider when evaluating tattoos for removal are: location, age and the skin type of the patient. (Kuperman-Beade & Levine, 2001)
A tattoo is made of particles of pigment injected into the skin. Although the body attempts to remove them, the particles of tattoo are too large to be removed and the body responds by encapsulating the whole tattoo in a wall of collagen that traps it within the skin permanently.? (Mohammad & Mahmood, 2009)
Tattoo ink particles are disrupted and broken up by the photomechanical and photothermal effects of laser energy, and it has been theorized that the optimal pulse width is within the picosecond range, allowing for a safer and more efficient procedure [8]. The recent addition of the alexandrite picosecond laser has shown great promise in rapid effective removal of blue and green inks. The exact mechanism of yellow pigment destruction remains unclear as no laser wavelength is available that directly targets the yellow chromophore, suggesting yellow pigment maybe more susceptible to the photomechanical effect  (Alabdulrazzaq, Brauer, Bae, & Geronemus, 2015)
Tattoo inks are composed of pigments that are suspended in a carrier solution. The tattoo pigments range from inorganic materials to azo dyes, with variable absorption spectra.[2,3] They are primarily metal salts but can also be an assortment of plastics and vegetable dyes [ Table 1]. The pigment provides the color of the tattoo. The carrier may be a single substance or a mixture. The purpose of the carrier is to keep the pigment evenly distributed in a fluid matrix, to inhibit the growth of pathogens, to prevent clumping of the pigment, and to aid in application to the skin. The most common ingredients in the carrier are ethyl alcohol, purified water, witch hazel, ListerineTM, propylene glycol, and glycerol. (Barua, 2015)
Q-switching, or quality switching, of a laser is a mechanism used to control the light output by concentrating all the energy into intense bursts or series of pulses by modulating the intracavity losses, the so-called Q factor of the laser resonator.   The technique is mainly applied for the generation of nanosecond pulses of high energy and peak power with solid-state bulk lasers. Laser devices that incorporate Q-switching are able to achieve selective photothermolysis due to their high energy and short-pulse duration. This can be applied in the setting of removal of the tattoo pigment to arrive at the desired clinical results without much damage to the surrounding tissues, and with relatively faster and uncomplicated healing time.[6]
The key requirement to laser tattoo removal is that the light must reach and be absorbed by the tattoo.  (Bernstein., 2006)
professional tattoos involve a wider variety of pigments that are placed deeply and densely into the dermis.[1,2,3] This creates challenges in selecting the appropriate laser and achieving complete clearance. (Sardana, Ranjan, & Ghunawat, 2015)
Professional tattoos are notorious for their wide range of undocumented chemical compositions and will continue to pose therapeutic challenges, (Sardana et al., 2015)
Q switching is a means of producing a very short laser pulse in the nanosecond domain.  (E.F Bernstein, 2006)
Anderson and Parrish,47 in their seminal article describing the concept of selective photothermolysis, which is the ability to remove target tissues in skin without hurting the surrounding unaffected skin, state that small targets are best treated with pulses in the nanosecond range. (E.F Bernstein, 2006)
Q-switched lasers have become, and remain, the mainstay of modern tattoo removal. There are three types of Q-switched lasers: the ruby, alexandrite, and neodymium:yttrium-aluminum- garnet (Nd:YAG) lasers. (E.F Bernstein, 2006)
Typically, ruby lasers have been very effective at removing black and dark blue tattoo pigments (Fig. 5). In addition, amateur, traumatic, and medically placed tattoos used as markers for administering radiation therapy respond quite well to the Q-switched ruby laser.  (E.F Bernstein, 2006)
In general, there are five categories of tattoos: professional, amateur, cosmetic, medicinal, and traumatic.
It is important to note that there are considerable differences between the three available laser wave- lengths used for tattoo removal.The Q-switched ruby and alexandrite lasers are optimal for removing black, blue and green pigments; the Q-switched 532 nm Nd:YAG laser can be used to remove red pigments; and the 1064 nm Nd:YAG laser is ideally used for removal of black and blue pigments (Jow et al., 2010)
New laser technology discussed briefly
Combination laser treatment Non-ablative or ablative fractional resurfacing has been reported to be effective for tattoo removal, either when combined with QS ruby laser treatment or as monotherapy.   (Ho & Goh, 2015)
Multi-pass treatments e R20 method of tattoo removal, where accelerated lightening can be achieved by using four laser passes in one treatment session, with an interval of 20 min between the passes.[38] The 20 minutes waiting time allows for the post-laser immediate whitening to resolve completely before a second pass is given. (Ho & Goh, 2015)
Monotherapy with QSL is often effective for tattoo removal but combining QS laser with an ablative fractional laser or nonablative fractional laser may yield faster clearing, minimize number of sessions, and reduces side effects. The combination can be in any order; FL followed by QSL helps reduces blister formation.  (Shah, 2015)

Pulse diameter (Picosecond lasers) Most tattoo pigments have a particle size of 30-300 nm, corresponding to a thermal relaxation time of less than 10 nanoseconds.[18] Thus an ideal laser should have a pulse duration in nanoseconds, which is the logic of using QS lasers (10-9 s). Newer laser technologies shorten that pulse time to picoseconds (10-12 s), promising more effective results in tattoo removal. (Sardana et al., 2015)
But pulsed lasers like Er:YAG and the ultrapulsed CO2 lasers can be used to precisely remove epidermal layers. [29,30] This was studied using a combination of ultrapulse CO2 laser followed by QS Nd:YAG,[29] in a split lesion design which lead to a significant reduction in the number of sessions with negligible side effects [Figure 3 ]. This has been further modified using the Er:YAG followed by the QS Nd:YAG with better results and has been christened the Rapid Tattoo Removal technique (RTR)  (Sardana et al., 2015)
Picosecond lasers
These lasers have been developed as the need for lasers with shorter pulse durations than the above Q-switched lasers, to decrease the number of treatments necessary to remove tattoos and optimize treatment (Choudhary, Leiva, & Nouri, 2010)
QS lasers emit short, high-intensity pulses that cause thermomechanical destruction via photoacoustic waves, leading to the fragmentation of tattoo pigments encased in intracellular lamellated organelles. The subsequent phagocytosis of fragmented ink particles results in gradual fading and clearance of the tattoo pigments. (Barua, 2015)
The concept of selective photo- thermolysis was explained by Anderson and Parrish as the ability to remove target tissues in skin without causing any damage to the surrounding tissues, by a given wavelength of laser light  (Choudhary et al., 2010)
The theory of selective photothermolysis plays an essential role in the laser tattoo removal process as the duration of light exposure must be less than the thermal relaxation time. Current Q-switched lasers are able to yield extremely short laser pulses with durations in the nanosecond range and there- fore permit the specific heat confinement needed for photoacoustic destruction of these pigments’ chromophores and particles.  (Jow et al., 2010)
The concept of selective photothermolysis revolutionized the treatment of tattoos by preferentially targeting the tattoo pigment with specific wavelengths and pulse durations of laser light that the tattoo ink particles selectively absorb while adjacent structures are left essentially unharmed.47 Tattoo ink particles are small and therefore require Q-switched (QS) laser systems with brief (nanosecond) pulse durations. The high energy delivered over an ultrashort time period results in shattering of the ink particles, which are then engulfed by tissue macrophages and cleared by the lymphatic system or through trans epidermal elimination. (Ortiz & Alster, 2011)
Newer techniques for tattoo removal involve combinations of QS pigment-specific (red and infrared) lasers with ablative fractional laser resurfacing, which have been reported to enhance the rate of pigment clearance and decrease risk of vesiculation.54?Other novel technologies include the picosecond laser, which has been shown to be better in tattoo pigment clearance than the nanosecond lasers in Yorkshire pigs (Ortiz & Alster, 2011)
Q-switched lasers with light having wavelength in the visible and near-IR region …… Because of the inhomogeneous distribution of the pig- ment in the skin, the strength of the laser-pulse tissue interaction varies even within a single tattoo (Cencic & Gregorcic, 2012)
There is a controversy in the literature surrounding the mechanism of tattoo pigment reduction in tissue. The two major mechanisms, which have been proposed for the fragmentation of tattoo ink granules, are thermal and acoustic. Though majority of studies have focused on fragmentation through thermal mechanisms,[4] some have suggested that the acoustic mechanism predominates in short pulsed laser therapy.[5,6] In contrast, Welch et al. [7] suggested that the laser-induced damage may be caused by a combination of thermal and acoustic effects. Accordingly, a wide range of predicted optimal parameters for laser treatment have been suggested, which make the settings and parameters subject to variation.
The ultimate goal is to minimise sessions and maximise results. Total clearance of a tattoo is not often seen and one study reported that only three of 238 paying patients achieved this goal.[8] Thus, a constant endeavour is to optimise laser parameter selection, increase the efficacy of each treatment session, and minimise the total number of treatment sessions required.[1,2,8] (Sardana et al., 2015)
The number of treatment sessions also depends on pigment colour, composition, density, depth, age of the tattoo, body location and the amount of tattoo ink present. (Sardana et al., 2015)
More recently placed tattoos with deeply located pigment on a distal site are harder to remove due to the reduced lymphatic distribution which helps in removing residual ink particles (Sardana et al., 2015)

selective photothermolysis. This implies that the laser causes targeted destruction of the tattoo pigments by means of selectively absorbed wave- length and a pulse duration shorter than the thermal relaxation time (the time a structure needs to cool down to half the temperature to which it was heated). This would result in only minimal damage to the epidermis, dermis, and skin appendages, while selectively destroying the target pigment, which acts as the chromophore for the laser  The tattoo ink is an exogenous chromophore.
Q-switching is a technique that produces nanosecond laser pulses by suddenly releasing all of the excited-state energy from a laser medium. A whitening reaction occurs upon exposure to this laser. (Choudhary et al., 2010)
Anderson and Parrish, in their landmark papers on skin optics,[7,8,9] propounded the theory of selective photothermolysis. This theory postulates that light of a wavelength that is absorbed by a target chromophore will selectively damage or destroy that chromophore if the fluence is sufficiently high and the pulse duration is less than or equal to the thermal relaxation time (TRT) of that chromophore. It follows, therefore, that if the laser pulse duration is less than the TRT of the target chromophore, heat diffusion does not take place and the damage is selectively confined to the target without any collateral injury to the surrounding tissues.
QS lasers work on the principle of selective photothermolysis and also produce an additional photoacoustic effect, producing shock waves that cause explosion of the target.[8,10,11] Very high energy to the tune of 300 MW is delivered in a very short period of time (5- 100 ns), which leads to rapid thermal expansion. This produces shock waves that rupture the targeted ink particles.[12,13] Phagocytosis of the pigment by macrophages is the primary method of elimination. The ruptured fragments are directed by tissue macrophages either to the lymphatic channels or to the regional lymph nodes. Some fragments may be transepidermally eliminated as the posttreatment crust is sloughed off.[5,14]  (Barua, 2015)
the skin contains three major chromophores—hemoglobin, melanin, and water—lasers that are absorbed strongly by these wave- lengths would have to compete with these chromophores for absorption. Thus, the competing chromophores of melanin, hemoglobin, or water would take up some of the laser energy not allowing it to reach the tattoo granules. Currently available Q-switched lasers are ideal for tattoo removal in the sense that they are absorbed poorly by competing chromophores and penetrate deeply. (E. F. Bernstein, 2007)

3.    The mechanism of action of laser tattoo removal has been discussed in detail by considering laser-tissue interactions. – considering laser-tissue interaction.  Systemic interaction – lymphatics discussed.
Photothermolysis describes the ability to remove targets from within skin or other tissues without affecting the surrounding, uninvolved skin. These targets can be virtually anything that takes up laser energy such as blood vessels, melanin pigment, or tattoo particles. Anderson and Parish state that small particles such as tattoo granules should be treated with pulses in the nanosecond domain. (E. F. Bernstein, 2007)

To be selective, the pulse duration of the laser should match the TRT of the target. The estimated TRT of the epidermis is 1-10 ms and the TRT of the tattoo ink particles is 0.1-10 ns, although some newer estimates are in the range 10-100 ps.[5] The size of the tattoo ink particles is about 10-100 nm and is generally placed at a depth of 1.1-2.9 mm. Laser-tissue interaction produces intercellular steam and vacuole formation within the target pigment that cause a scattering of visible light, leading to immediate whitening. An audible popping sound is heard during the laser procedure due to the photoacoustic effect. (Barua, 2015)
There are several variables that influence tattoo removal using the QS lasers. Smoking, the presence of colors other than black and red, a tattoo larger than 30 cm2, a tattoo located on the feet or on the legs, one that is older than 36 months, one with a high color density, treatment intervals of 8 weeks or less, and the development of darkening phenomenon are associated with reduced clinical response rates.[17] (Barua, 2015)
The Kirby-Desai Scale is a useful index to correlate with the number of treatment sessions required for satisfactory tattoo removal. It is based on six tattoo criteria – skin type, location, color, amount of ink, scarring, and layering.[18]   (Barua, 2015)  (Kirby, Desai, Desai, Kartono, & Patel, 2009)
Tattoo-removing lasers must be absorbed by the tattoo granules to effect removal. Because today’s tattoo pigments come in a myriad of colors, multiple wavelengths of light may be required to remove a single tattoo. In addition to variations in color, tattoos may become resistant to certain wavelengths of light in a manner similar to bacteria becoming resistant to antibiotics. Thus, multiple wavelengths of light may be required to remove even the simplest of colors to treat, such as black, with minimal or no scarring.  (E. F. Bernstein, 2007)

Understand the variables involved in tattoo removal which are depicted in Figure 1 and Table 1. Three broad aspects are involved, the laser(s) used, the skin phenotype and tattoo dependant factors, which includes the type, depth and size of tattoo [Figure 1]. A rarely appreciated aspect of tattoo removal is the role of the host immune response, which ultimately phagocytoses the tattoo particles and drains them away via the lymphatics.  Thus it is the inflammation consequent to the laser therapy and the concomitant stimulation of the host response that ultimately results in removal of tattoo ink via the lymphatics.  (Sardana et al., 2015)
Tattoo pigments, which consist of insoluble, sub-micrometers – sized particles that are phagocytosed by dermal cells, react almost the same way as melanosomes. Tattoo particles, sometimes grouped in granules and packed into vacuoles from 0.1 to 10 microns in diameter, are endocytosed by fi- broblasts as well as macrophages in the dermis and sometimes in the subcutis.  (Adatto, 2004)
The absorbtion of light pulses by the tattoo pigments is the first and most important step. If there is no absorbtion, there is no reaction. Immediately after impact, the epidermis looks white which corresponds to gas forma- tion. This whitish colouration disappears spontaneously within minutes. The tattoos pigments absorb the short laser pulses, 10–9 sec, so called Q-switched (Adatto, 2004)
In- side the pigments, this light is converted into heat with- in nanoseconds, producing an increase in temperature above 1000 °C (photothermal effect). This rapid ther- mal expansion produces shock waves and a potential localized cavitation, so called photoacoustic shock which leads to a particle fragmentation and selective death of pigment containing cells. There is also at the same time a breaking in the chemical bonds inside the pigment (photochemical effect). The inflammatory reponse that follows this process probably engulfs the cells debris as well as the fragmented tattoo pigments. This process of inflammation and phagocytosis might reduce the overall amount of tattoo pigment into the dermis. These particles, as well as their decomposition products, are usually found in regional lymph nodes. Some of the fragmented particles stay in place within the dermis, but as they are redistributed by the laser photoacoustic shock, their dermal scattering coefficient changes and they look less visible to the naked eye as they are located deep in the dermis. Finally, the only part of the pigment which is really eliminated from the body is a very superficial one as it is eliminated by desquamation of epidermis during its repair (19, 20). This phenomenon is called transepidermal elimination. (Adatto, 2004)
Generally, tattoo pigments are comprised of inorganic and/or organic compounds, such as chromium, mercury, iron, copper, carbon, and polycyclic compounds. The diversified composition of tattoo pigments results in competing chromophores, usually with different absorption spectra
(Jow et al., 2010)
As the tattoo ages, the tattoo’s pigment granules become engulfed by resident dermal fibro- blasts and macrophages and can be found within their lysosomes. Ultimately, laser tattoo removal is accomplished by photoacoustic destruction of the tattoo particles.This leads to the formation of smaller fragments that can then be more easily removed via the vascular or lymphatic systems, re-phagocytosis by mononuclear cells, or elimination through the epidermis (Jow et al., 2010)
Q-switched lasers have now become the standard for removal of tattoos. However complications can occur.  On delivery of the laser in the skin, the energy that is absorbed by the pigment is converted to heat, which is the photothermal effect. There is breakage of chemical bonds inside the pigment, which is the photochemical effects. There is a mechanical destruction of the pigments due to photoacoustic effects. Small pigment particles, unknown decomposition products and newly generated chemical compounds are then removed from the skin via blood vessels or the lymphatic system (Khunger, Molpariya, & Khunger, 2015)

There are also structural changes noted in the pigment particles. Depending on the dosage, temporary whitening may occur during the treatment. Whitening is caused by rapid local heating of the pigment leading to gas or plasma formation and subsequent dermal and epidermal vacuolization. The whitening reaction appears immediately with the use of the laser and is replaced by a scab in 2–5 days. A test spot with the laser provides an opportunity to test the suitability of a particular laser for a skin phototype or tattoo response to laser treatment. The small test area can then be reevaluated in 1 month. Post-procedure patients must be instructed to apply a petrolatum-based emollient on the treated area until the scab falls off (Choudhary et al., 2010)
Temporary local side effects like erythema, burning, edema, crusting, and pain should be considered as a normal skin reaction following laser treatment. s laser treatment creates a superficial wound, especially immunosuppressed patients are at risk of developing local skin infections. A thorough medical history is mandatory before laser treatment to identify possible risk factors for such side effects.(Klein, Rittmann, & Hiller, 2013)

4.    One major complication specific to laser tattoo removal has been identified and discussed on a cellular level in great detail.
COMPLICATION
However side- effects and complications can result from laser attempts at removal such as scarring, infection, bleeding, hypopigmentation, hyperpigmentation, partial lightening and tattoo ink darkening. (Varma & Lee, 2002)

Side effects do occur, many of which are thermally mediated. The most frequently occurring temporary side effects of laser tattoo removal include pain, erythema, crusting, pinpoint bleeding, blistering, swelling, infection, and pigmentary disorders. Permanent side effects include mainly scarring, hypo- or hyperpigmentation, and color change of tattoo pigment(Klein et al., 2013)
Risk factors for the development of side effects are darker skin type, tanning, intake of photosensitizing agents, and a predisposition to develop hypertrophic scars or keloids. Furthermore, applying the wrong wavelength or non-appropriate pulse durations might lead to severe side effects (Klein et al., 2013)
Side effects and limitations of laser tattoo removal include the need for multiple treatment sessions, risks for hypo- and hyperpigmentation, post-treatment bleeding, blistering, and infection, and textural changes. Hypopigmentation most commonly occurs with the Q-switched ruby laser, whereas hyperpig- mentation is more commonly seen with all Q-switched lasers when darker skin types are treated (Jow et al., 2010)
As the treatments can be painful, time-consuming, and costly, many patients become discouraged over the course of their treatment many truncate the number of their sessions, resulting in inadequate results. Thus, it is important to evaluate the issues affecting patient compliance and its overall impact on the success rates of laser tattoo removal
(Jow et al., 2010)
The complications of laser tattoo removal can be divided into immediate and delayed (Khunger et al., 2015)
Immediate include pain, blisters [Figure 4], crusting and pinpoint haemorrhage [Figure 5]. These are more common in darker skins, using a high fluence.  (Khunger et al., 2015)
The most common delayed complication is pigmentary changes, either hypopigmentation [Figure 6] or hyperpigmentation. These occur 4-6 weeks after laser treatment and most of them are transient. However, longer- lasting pigmentary alterations can occur, especially in darker or tanned skin.  (Khunger et al., 2015)
Hypopigmentation. In addition to the interaction with tat- too pigments, quality-switched laser devices destroy melanosomes in the skin, which are similar in size and cellular location as tattoo pigments. The greater melanin absorption seen with shorter wavelengths increases the risk of hypopigmentation. This occurs in about 5–10% of the cases11,12 and is mostly transient, but can be permanent;13 it is also more closely related to the main effect – pigment removal – than to an actual side effect and thus not limited to false usage of the laser.  (Karsai, Krieger, & Raulin, 2009)

There has been a exponential increase in decorative tattooing as a body art in teenagers and young adults. Unfortunately there are no legislations to promote safe tattooing, hence complications are quite common. Superficial and deep local infections, systemic infections, allergic reactions, photodermatitis, granulomatous reactions and lichenoid reactions may occur. Skin diseases localised on the tattooed area, such as eczema, psoriasis, lichen planus, and morphea can be occasionally seen. (Khunger et al., 2015)
Acute complications include pain, blistering, crusting and pinpoint hemorrhage. Among the delayed complications pigmentary changes, hypopigmentation and hyperpigmentation, paradoxical darkening of cosmetic tattoos and allergic reactions can be seen. Another common complication is the presence of residual pigmentation or ghost images. Scarring and textural changes are potential irreversible complications (Khunger et al., 2015)
These occur mainly due to the unsterile pigments that are implanted and unsterile conditions in which they are carried out. Different reactions have different times of onset as few of them appear immediately after the procedure and some may take days to weeks to years to appear (Khunger et al., 2015)
The most commonly reported reactions were tenderness and itching associated with allergic reactions and bumps secondary to granulomatous reactions.2  (Ortiz & Alster, 2011)
The lichenoid pattern is the most common and is thought to represent a delayed hypersensitivity reaction (Ortiz & Alster, 2011)

Cutaneous lymphoid hyperplasia (CLH)
CLH or pseudolymphoma comprises of a heterogeneous group of benign T- or B-cell lymphoproliferative reactions that are either idiopathic or associated with stimuli such as drugs or contact dermatitis. Approximately 20 cases of tattoo-induced CLH have been reported to date where they have occurred as asymptomatic or itchy, single or multiple, nodules or swellings [8–12]. It is mostly related to red color, but associations with blue and green are also known. This reaction can greatly resemble a lichenoid or granulo- matous reaction [7]. The most recent report on CLH in tattoos was a case series of seven patients who developed CLH with tattoos. Their skin biopsies and contact test were performed and suggested a combined T- and B- cell response [13]. To date, only one case of lymphoma developing in CLH in a tattoo has been reported (Choudhary et al., 2010)

One of the most common mistakes novice laser surgeons make is increasing the laser fluence in refractory tattoos by shrinking the spot size. This places more of the administered energy superficially in the skin, resulting in a greater chance of scarring and side effects  (Bernstein., 2006)
This is as the laser merely works by disruption of the tattoo and it is the host tissue response that effects the phagocytosis and expulsion of the tattoo from the skin via the lymphatics.[3,4,26] Patients suffering from short- and long-term immunosuppression (i.e., via chemotherapy, drug-induced, or a medical condition) may experience poor healing, which can further lead to ink retention following laser treatments.[41] This is specially relevant in patients on oral steroids, azathioprine and cyclophosphamide, often prescribed by dermatologists.
Individuals presenting with underlying immunosuppression should be referred to the appropriate specialist for comprehensive care. Once the condition has stabilised or resolved, they should be considered appropriate candidates for laser tattoo removal treatment (Sardana et al., 2015)

Dyspigmentation and textural changes
As melanin is the main competing pigment when treating tattoos with Q-switched lasers, increased melanin absorption with shorter wavelengths has resulted in hypopigmentation [50, 53]. This may be transient (seen with 510- and 532-nm lasers) or long-term (seen with QSRL). Gundogan et al. [54] treated hypopigmented areas that had remained unchanged for over 4 years after tattoo removal with the Q-switched Nd: YAG laser, using the 308-nm xenon-chloride excimer laser. It induced a significant repigmentation in 40 sessions over 14 months. The excimer laser has the potential to influence the reduced activity of the melanocytes, as was demonstrated with electron microscopy.
Hyperpigmentation is another concern more in the darker-skinned individuals, so they can be better treated with the Nd:YAG laser, the longer wavelength of which better spares the epidermis. If QSRL or Q-switched alexandrite lasers must be used, then it should be compensated by lower fluences. Also, dark-skinned and tanned individuals should be treated with bleaching agents before initiating laser treatment. Additionally, in patients prone to pigmentary and textural changes, longer treatment intervals may be helpful. Patients should avoid sun- exposure. Treatment may consist of hydroquinone and regular use of sun protection. Fractional photothermolysis may be considered  (Choudhary et al., 2010)

5.    A discussion indicating how complications and side effects of laser tattoo removal in general may be minimized in clinical practice.
With the increasing incidence of tattooing as a fashion trend in society, clinicians should be able to recognise and treat those complications at the earliest and also appropriately counsel their patients on risks of tattoo placement. Thorough clinical history and examination are essential to make a diagnosis. To confirm the diagnosis, skin biopsy is mandatory, especially with a papulonodular growth within the tattoo pigment, since neoplastic conditions are not immediately recognised with clinical examination only.  (Khunger et al., 2015)
The laser should be chosen according to the colour of the tattoo pigment and the patient’s skin type. Generally Q- switched 1064nm Nd:YAG laser is safer in darker skin types 5-6. The spot size, the fluence and the pulse duration are important and should be carefully selected. (Khunger et al., 2015)
Risk factors for the development of side effects are darker skin type, tanning, intake of photosensitizing agents, and a predisposition to develop hypertrophic scars or keloids. Furthermore, applying the wrong wavelength or non-appropriate pulse durations might lead to severe side effects (Klein et al., 2013)
Sun avoidance is an important measure to prevent side effects when performing laser therapy as the epidermal mel- anin competes for absorption of laser light in skin. If a patient is suntanned, treatment should be delayed or a Q-switched Nd:YAG laser should preferably be used due to its longer wavelength. Hypopigmentation is a frequently described side effect of laser therapy. Fitzpatrick et al. [15] described hypopigmentation in 50 % of patients after Q-switched alexandrite laser tattoo removal, which is in accordance with our results. These pigmentary changes might be transient(Klein et al., 2013)

6.    CONCLUSION
Laser treatment requires multiple painful sessions that are expensive and sometimes incompletely successful. With an increase in the number of ink colors, tattoo removal is becoming increasingly difficult.  (Ortiz & Alster, 2011)
Although the Q-switched lasers are capable of removing tattoos without harming the skin, removal often takes numerous treatments and still can be incomplete, especially when attempting to remove multicolored tattoos. Developments leading to removable tattoo inks, feedback systems to detect the absorbance characteristics of tattoo inks, dermal clearing agents, and perhaps even shorter pulse-duration lasers should result in improvements in tattoo removal in the near future. (E. F. Bernstein, 2007)

There are still many improvements that can be made in the field of laser tattoo removal to increase the efficacy of these treatments so that results can be obtained faster and prove more tolerable for the patients. Such advances include new research in pico- and femto-second lasers as well as the development of laser-susceptible tattoo inks.
(Jow et al., 2010)

QS lasers, based on the principle of selective photothermolysis, provide for techniques of tattoo removal that achieve selective removal of each tattoo pigment with minimal risk of scarring and/or pigmentary alteration. Since many wavelengths are needed to treat multicolored tattoos, a single laser system cannot be used alone to remove all the available inks and its combinations. Several studies[24,25] have concluded that picosecond pulses are more efficient than nanosecond pulses at tattoo particle fragmentation. Current research is, therefore, focusing on newer picosecond lasers, which may be more successful than the QS lasers in effective and rapid clearance of the new vibrant tattoo inks. (Barua, 2015)

Stop and think before you ink holds very much true in the present scenario. (Khunger et al., 2015)

It has been rightly sung by Jimmy Buffett, an American singer that a tattoo is a permanent reminder of a temporary feeling. (Khunger et al., 2015)

Bibliography

Adatto, M. A. (2004). Laser Tattoo Removal- Benefits and Caveats. Medical Laser Application, 19, 175-185.
Alabdulrazzaq, H., Brauer, J. A., Bae, Y. S., & Geronemus, R. G. (2015). Clearance of yellow tattoo ink with a novel 532-nm picosecond laser. Lasers Surg Med, 47(4), 285-288. doi:10.1002/lsm.22354
Barua, S. (2015). Laser-Tissue Interaction in Tattoo Removal by Q-Switched Lasers. Journal of Cutaneous and Aesthetic Surgery, Volume 8(1), 5-8. doi:10.4103/0974-2077.155063
Bernstein, E. F. (2006). Laser treatment of tattoos. Clinics in Dermatology, 24, 43-55. doi:10.1016/j.clindermatol.2005.10.025
Bernstein, E. F. (2007). Laser Tattoo Removal. Seminars in Plastic Surg, 21(3), 175-192. doi:10.1055/s-2007-991186
Bernstein., E. F. (2006). Laser treatment of tattoos. Clinics in Dermatology, 24, 43-55. doi:10.1016/j.clindermatol.2005.10.025
Burris, K., & Kim, K. (2007). Tattoo removal. Clinics in Dermatology, 25, 388-392. doi:10.1016/j.clindermatol.2007.05.011
Cencic, B., & Gregorcic, P. M. i., J. Jezers?ek, M. (2012). Laser tattoo removal as an ablation process monitored by acoustical and optical methods. Applied Physics A Material Science & Processing, 112, 65-69. doi:10.1007/s00339-012-7203-0
Choudhary, S. E., M.L., Leiva, A., & Nouri, K. (2010). Lasers for tattoo removal- a review. Lasers in Medical Science, 25, 619-627. doi:10.1007/s10103-010-0800-2
Ho, S. G., & Goh, C. L. (2015). Laser tattoo removal: a clinical update. J Cutan Aesthet Surg, 8(1), 9-15. doi:10.4103/0974-2077.155066
Jow, T., Brown, A., & Goldberg, D. J. (2010). Patient compliance as a major determinant of laser tattoo removal success rates: A 10-year retrospective study. Journal of Cosmetic and Laser Therapy, 12, 166-169. doi:10.3109/14764172.2010.503787
Karsai, S., Krieger, G., & Raulin, C. (2009). Tattoo removal by non-professionals – medical and forensic considerations. JEADV Journal compilation ª 2009 European Academy of Dermatology and Venereology, 24, 756-762. doi:10.1111/j.1468-3083.2009.03535.x
Khunger, N., Molpariya, A., & Khunger, A. (2015). Complications of Tattoos and Tattoo Removal: Stop and Think Before you ink. J Cutan Aesthet Surg, 8(1), 30-36. doi:10.4103/0974-2077.155072
Kirby, W., Desai, A., Desai, T., Kartono, F., & Patel, G. (2009). The Kirby-Desai Scale- A Proposed Scale to Assess Tattoo-removal Treatments. The Journal of Clinical & Aesthetic Dermatology, 2(3), 32-37.
Klein, A., Rittmann, I., & Hiller, K.-A. L., M. Ba¨umler, W. (2013). An Internet-based survey on characteristics of laser tattoo removal and associated side effects. Lasers Med Sci. doi:10.1007/s10103-013-1395-1
Kuperman-Beade, M., & Levine, V. J. A., R. (2001). Laser Removal of Tattoos. American Journal Of Clinical Dermatology.
Mohammad, F. A., & Mahmood, A. S. (2009). Removal of Tattoo By 1064 and 532nm Q-switched Nd- YAG laser. Iraqi Journal of Medical Sciences, 7(3), 66-81.
Ortiz, E., & Alster, T. S. (2011). Rising Concern over Cosmetic Tattoos. American Society for Dermatologic Surgery, Inc., 38(3), 424-429. doi:10.1111/j.1524-4725.2011.02202.x
Sardana, K., Ranjan, R., & Ghunawat, S. (2015). Optimising laser tattoo removal. J Cutan Aesthet Surg, 8(1), 16-24. doi:10.4103/0974-2077.155068
Shah, S. D. A., S.J. (2015). Newer Trends in Laser Tattoo Removal. Journal Cutaneous Aesthetic Surgery, 8(1), 25-29. doi:10.4103/0974-2077.155070
Varma, S. S., N.A., & Lee, K. K. (2002). Tattoo ink darkening of a yellow tattoo after Q-switched laser treatment. Clinical & Experimental Dermatology(27), 461-463.