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Home , Cherry angioma, Infantile hemangioma, Jugular vein ectasia, Spider angioma

Lithuanian University of Health Sciences MEDICAL ACADEMY Faculty of Medicine Department of and Venereal Diseases

THE INDICATIONS AND EFFICACY OF ND:YAG LASER IN FOR VASCULAR DISORDERS

Author: María Esther Molina Osorio Supervisor: Assoc. prof. Vesta Kučinskienė

1 KAUNAS, 2018

INDEX

1.ABSTRACTS ...... 3

2.INTRODUCTION ...... 3

3. AIM AND OBJECTIVES ...... 7

4.MATERIAL AND METHODS ...... 7

5. RESULTS ...... 12

6. DISCUSSION ...... 13

Venous malformations ...... 13 malformations ...... 14 Port wine stains ...... 14 Teleangiectasias...... 15 Hereditary Hemorrhagic Teleangiectasia ...... 17 ...... 18 Cherry ...... 20 ...... 21 ...... 21

7. CONCLUSION ...... 22

8. REFERENCES ...... 22

2 Index of abbreviations Abbreviations Meaning GNAQ Guanine nucleotide-binding protein G(q) subunit alpha HHT Hereditary Hemorrhagic Teleangiectasia IH Infantile IPLS System KTP Potassium-titanyl-phosphate Nd:YAG Neodymium-doped yttrium aluminium garnet PDL Pulsed dye laser

1.ABSTRACTS

Different lasers modalities can be used for vascular treatment. But it is necessary to analyse which are the indications of Nd:YAG laser, and its applications on the dermatological field covering the main vascular lesions. This will include some comparative analysis between the efficacy of this laser and other laser’s modalities as well as it outcomes, the most common adverse events and average number of sessions indicated for each treatment. Key words: “Nd:YAG laser”; “Vascular lesions”; “Laser Therapy”.

2.INTRODUCTION

The emergence of lasers has supposed a significant advance in the treatment of multiple dermatological lesions. The origin of LASER acronym for Light Amplified of Stimulated Emision by radiation application in medicine appeared in the sixties, after the fabrication of the first ruby laser in 1960 by Theodor Maiman[1]. Leon Goldman was the precursor in the introduction of laser in medicine as he was the first one in applying this sort of technology in dermatology. At the beginning of his research Goldman studied the selective destruction of some pigmented structures in the skin and the study was recorded as “EFFECT OF THE LASER BEAM ON THE SKIN” (1963). The study was conducted with ruby laser in rabbits and some caucasian and

3 black volunteers.[2] Goldman continued his studies in the laser field paying importance to protective measures in the usage of these devices, as well as the need for personal eye protection. In 1973 he introduced Nd:YAG laser for the treatment of vascular lesions[3,6]. According to the different wavelengths used they were able to reach different regions on the skin. By the ‘80s three main laser equipment appeared with more specific value: CO2 laser, Nd:YAG and pulsed dye laser. The first two were mainly used for coagulation and cut and their first applications were in the field of otorhinolaryngology where they were mainly used as scalpels [4].

Nd:YAG laser neodymium-doped yttrium aluminium garnet is a solid state laser which means it requires a crystal as a medium for creating the source of light (this crystal is yttrium aluminium garnet (Y3Al5O12)). Lasers are doped with rare-earth ions and in the case of Nd:YAG laser the dopant, which is a substance in charge for alter the electrical or optical properties of a laser, is a triply ionized neodymium.[5,7]

The emission of Nd:YAG laser is of double frequency, with 1.064 nm and 532 nm of wavelength and applying with some dyes of solid polymers, wavelengths of 585 nm in yellow and 650 nm in are obtained. These frequencies allow the treatment of vascular lesions as well as permit tattoo removal of different colours [8]. Nd:YAG lasers operate in both pulsed and continuous mode. Pulsed Nd:YAG lasers are typically operated in the so-called Q-switching mode which is more powerful than continuous wave and is able to emit short pulses of light with high energy potential. Pulsed lasers can lead to more selective photothermolysis by its action on the chromophore[5] and they are useful treating vascular lesions which are usually very concerning for patients, becoming a prevalent reason for consultation, especially if they are in the facial region as facial , , port wine stains, hemangiomas, cherry hemangioma or . Also Nd:YAG laser has proven its efficacy in treating large and deep dilated in the lower limbs. Certain lasers can act selectively on the haemoglobin contained in the vessels, according to their localization different wavelengths are necessary for its penetration, that is why superficial lesions are more beneficed with some kind of lasers rather than with another, and this one of the cornerstone of the modality’s choice in treating lesions

4 Continuous mode of Nd:YAG laser is in contrast to pulsated mode, a continuous beam of light that enables a stable delivery of energy, this mode of laser is not commonly used in treatment of vascular lesions and there is not literature describing the application of this mode. The efficacy of Nd:YAG laser in vascular lesions is based on the wavelength; shorter waves like those of Alexandrite 755 nm laser present more affinity to melanin and are useful for hair removal[9], instead Nd:YAG 1064 nm (aproximately 8 mm of penetration) is more effective in deeper localizations. In the case of vascular lesions blood vessels are the target and the chromophore is the hemoglobin. Water that is present in the cells acts as an additional chromophore [5].

Nowadays the main lasers used for the treatment of vascular lesions are:

Table 1. Main lasers used in vascular lesions treatment.[10] Laser Light Wavelength Target Applications spectrum (nm) KTP Greenlight 532 nm Oxyhemo- -Facial teleangiectasia globin -Diffuse erythema -Cherry and spider -PWS -Thin leg teleangiectasia (< 1mm) PDL Yellow 585-595 nm Oxyhemo- -Facial teleangiectasia globin -Rosacea - -PWS -Thin leg teleangiectasia (<1 mm) Alexandrite Infrared 755 nm Melanine -PWS -Wider leg teleangiectasia Diode Infrared 800-983 nm Melanine -Facial teleangiectasia -PWS -Leg teleangiectasia -Venous lakes Nd:YAG Infrared 1064 nm Oxyhemo- -PWS globin -Larger leg teleangiectasia -Venous malformations -Infantile hemangioma -Pyogenic granuloma

5 IPLS Mostly 500-1200 -Facial teleangiectasia used in nm -Diffuse erythema yellow and -Rosacea red -PWS -Fine leg teleangiectasia

Chart 1. Skin penetration of different lasers 1200

1000

800

600

400 Skin penetration (nm) penetration Skin 200

0 KTP PDL Ruby Alexandrite Diode Nd:YAG Main lasers in dermatology

Vascular lesions are skin lesions arising from blood vessels, there are multiple classifications according to ISSVA (International Society for the Study of Vascular Anomalies) they classify vascular lesions into vascular tumors and vascular malformations, the formal classification include more lesions, but in the following table are the main ones:

Table 2. Classification of vascular lesions.

BENIGN VASCULAR TUMORS VASCULAR MALFORMATIONS Infantile hemangioma Venous malformations Congenital hemangioma Combined vascular malformations simple Pyogenic Granuloma Capillary malformations: -Port wine stains -Teleangiectasias

6 In this review, the focus of study will be Teleangiectasia, Hemangiomas, Port Wine stains, angiokeratoma, , pyogenic granuloma and venous malformations, as they the focus of study in relation to Nd:YAG laser.

3. AIM AND OBJECTIVES

To review applications and indications of Nd:YAG laser while treating vascular lesions. This will include some comparatives analysis between the efficacy of this laser and others laser’s modalities as well as it outcomes, the most common adverse events and average number of sessions indicated for each treatment.

4.MATERIAL AND METHODS

For the development of this research articles were included from PubMed and Cochrane for identifying eligible studies. Some studies were selected for inclusion, assessed the methodological quality and extracted data. Articles were carefully chosen from the last ten years (2006 till nowadays) Different combinations of words were included for searching purposes. Key words were: “Nd:YAG laser”; “Vascular lesions”; “Laser Therapy”. Afterwards, the research has been amplified including other key terms in relation to the topic “Infantile hemangioma”; “Port wine stain”; “Leg veins”; “Venous malformations”; “Pyogenic granuloma”; “Teleangiectasia”; “Cherry angioma”; “Solitary angiokeratoma”; “Hemangiomas”. Inclusion criteria: 1. Nd:YAG laser compared to others laser modalities. 2. Case series and studies. 3. Previous reviews. Exclusion criteria: 1. Animal studies. 2. Other organs different from the skin. 3. Vascular lesions in oral cavity. 4. Laser treatment in dark skin patients.

7 After identification of the articles suitable for this review, that accomplish the previous mentioned criteria and for a better selection and revision of them, a critique and compressive reading was performed, in order to elaborate a small report about the efficacy of Nd:YAG laser in treatment of different vascular lesions, as well as other parameters that plays a role in its use. Discarding those referenced that were not relevant for this review.

Overall publications for selected keywords. N= 205

Excluded by exclusion criteria N=140

Results for first

screening N=65

Screening of full text articles N= 29

Excluded due to not direct relation to the topic N= 13

Final selected articles N=16

Prospective Retrospective studies N=8 studies N=8

-Figure 1: Flowchart of searching methodology

8 Table 3. Summary of studies regarding Nd:YAG and its application in vascular lesions Study Type of Nº of Female Age Vascular lesions Localization Energy Average Follow Adverse reactions reference study patients (n) (Mean) applied Nº of up (J/cm2) sessions Lee JH. RS 12 7 43± 5,8 Telangiectasia Nasal tip 216,7-261, 4 1 12 weeks Vesicles 2012 years Alae nasal J/cm2 [11] Eui H. RS 14 9 45,4 Port wine stains Face 214,2- 1 1 month Erythema 2015 years Haemangioma 252,2J/cm2 Vesicles [12] Acne erythema Hyperpigmentation Cherry angioma Moha- PS 2 1 29 Venous Forehead 100-800 J 1 >2 years Redness mmad R. years malformation discoloration 2016 [13] Zeleayi RS 1 1 13 Solitary Right upper 80-130 J/cm2 2 3 months Not reported K. 2015 years angiokeratoma leg [14] Murtad- PS 16 16 21 Port wine stains Not specified 30 J/cm2 12 3 months Transient erythema ha H. years Scaliness 2016 Burning sensation [15] postsessions Lucian PS 25 21 45 years Telangiectasia Face NY: 80-150 4 1 year Hyperpigmentation F. 2006 Cherry angioma Legs J/cm2 (Nd:YAG) [16] Leg veins IPL: 15-38 J/cm2 A. PS 4 2 69 years HHT (Osler’s Palms 120-220 Not 8 weeks Slight atrophy Werner disease) Face J/cm2 specified Hypopigmentation 2008 [17]

9 Stefan H. PS 20 10 38 years Pyogenic Head 60-180 J/cm2 1-4 > 6 Pain 2012 granuloma Extremities months formation [18] Abdomen B. Parlar PS 56 56 46 years Telangiectasia Legs 100-200 2 6 months Hyperpigmentation 2015 Reticular veins J/cm2 [19] Gunseli PS 45 18 52 years Cherry angioma Chest NY: 350 2 - Erythema S. 2011 J/cm2 Edema [20] KTP: 18 Pain J/cm2 Scar formation Kemal RS 255 189 35 years Face 180-340 Up to 5 5 months Pain and erythema O. 2012 Facial J/cm2 Severe urticarial [21] teleangiectasia Legs reaction Leg telengiectasia Hands Focal Bulla formation Erosion and crusting Transient postinflammatory hyperpigmentation M. U. PS 15 14 33 years Spider angioma Face 90-120 J/cm2 1 1 month Pain Anwar Leg Legs Scaling 2008 teleangiectasia Redness [22] D. Perru- RS 17 8 13,2 years Port wine stains Face PDL:6-9 5 2 months Purpura resolved choud Extremities J/cm2 after 2 weeks 2017 Trunk NY: 20-60 [23] J/cm2

10 Shu-xia RS 794 479 3,6 Infantil Head, face, 3-300 J/cm2 5 12 Pigmentation Z. 2015 months hemangioma neck, months disorders [24] extremities, Skin atrophy trunk, genital Wrinkled reductant area skin Kjell RS 38 24 4,5 Infantil PDL: 9 J/cm2 1-5 6 weeks Blistering M.K. months hemangioma Nd:YAG:90 Scarring 2014 J/cm2 [25] F. Hart- RS 149 107 24 weeks Infantil PDL:9-14 1-7 6 weeks Blistering mann hemangioma J/cm2 Crusts 2017 Nd:YAG:90- [26] 170 J/cm2 *Abbreviations: RS: Restrospective study; PS: Prospective study; NY: Nd:YAG laser; HHT: Hereditary haemorrhagic telangiectasia; IPL: Intense Pulse Light; PDL: Pulse dye laser; KTP: Potassium-titanyl-phosphate.

11 5. RESULTS

After a comparison between articles, Nd:YAG laser effective results are encountered in the treatment of leg and facial teleangiectasia, hemangiomas, infantile haemangioma, portwine stains, cherry angiomas, pyogenic granuloma and venous malformations. (Recorded in Table.3). Deep and resistant lesions are successfully treated with Nd:YAG in comparison to other lasers. Even though Nd:YAG laser has demonstrated its efficacy in the previously mentioned vascular lesions, for some pathologies other methods are preferred over Nd:YAG as in the case of leg teleangiactasia, where sclerotherapy presents the advantage of treat also feeder veins[19], or in the case of port wine stains treatment were PDL is the preferred modality[23]. The main localization for treated lesions is the face, followed by legs, chest and other regions. Energy delivered in the procedure varies between lesions and practitioners preference, maximal exposure according European Guidelines of care for vascular laser and intense pulse light sources[10] is 600 J/cm2 which is a common parameter in vascular . In one study conducted for treatment of cherry angioma [20] the energy applied increases until 350 J/cm2. Number of sessions range from 1 till 12. Average number of sessions among studies: 3 sessions. According to the follow up the minimal interval described is 6 weeks. Follow up period depends on subjective desire of the practitioners. Regarding side effects of laser treatment transient erythema, redness discoloration, burning sensation are reported early after treatment. Vesicles, pigmentation disorders commonly hyperpigmentation, slight atrophy or scar formation. All these adverse events eventually disappear with time. As disadvantage any patients report pain during procedure, and this laser increase risk of thermal injury to adjacent areas so qualified staff should provide treatment. It is important to mention the protective factors that are used during and after the procedure: -Avoid sun exposure pre- and after treatment, or use sunscreen in the affected area.

12 -Use of cooling devices that minimalizes irritation -Avoid overlapping pulses in same area as this increases the risk of scarring formation -Use of ice packs to diminish the oedema just after treatment is also recommended

6. DISCUSSION

Vascular lesions are usually concerning for patients, and have become a prevalent reason for consultation, especially if they are in the facial region as facial telangiectasia, port wine strains, hemangiomas, cherry hemangioma or acne erythema. They can be treated with Nd:YAG laser, and it has also proven its efficacy in treating large and deep dilated veins in legs.

The standard laser therapy for vascular lesions are PDL and IPL which is not discussed in this review, but these modalities are mainly adequate for superficial lesions, when we have deeper or larger lesions long pulsed durations laser as Nd:YAG can manage them more efficiently, but the long-term effects of long pulse therapy haven’t been evaluated so far. In this review long-pulsed Nd:YAG is achieved by 1064 nm or in some cases by 1444 nm[13] or 532 nm[15].

During this discussion, a comparison between different studies’ results while treating specific vascular disorders is presented.

Venous malformations are non-malignant lesions, usually present at birth; they have low-flow vascularization, hemodinamically insignificant. They usually appear at birth and get worse with age. They have predilection for the face and neck but can appear in any part of the body, in venous malformations we can distinguee between pure and combined, both of them have subsequent subdivisions. Vascular malformations treatment options include surgical excision, which is not strongly recommended due to the risk of profuse and scar formation or recurrence, laser therapy, sclerotherapy or intralesional bleomycin injection include other options. It exists a limitation in the number of publications related to this topic in conjunction with Nd:YAG laser therapy.

13 In a study [13] performed in 2016 the authors present two cases of patients treated with intralesional laser therapy, laser tip of fibreroptic 1444 nm Nd:YAG was introduced into the malformations previously anesthesiated, high energy was required for resolution of these lesions 800-1000 J, only 1 session was needed and after treatment redness of less than 48 hours of duration was encountered. After 2 years results were quite satisfactory. Fiberoptic Nd:YAG laser is an effective and safe treatment alternative, but more researches and controlled studies are needed with greater population.

Capillary malformations

Port wine stains (nevus flammeus) are congenital malformations arising from mutations of somatic origen in certain genes as GNAQ. They are therefore associated with some genetic syndromes as Sturge-Weber syndrome or Klippel-Trenaunay-Weber syndrome; PWS related to these syndromes are more refractory to treatment. They receive its name due its similarity with a Portuguese wine. Port wine stains present variable size arising predominantly in the face and neck even though they may appear in any part of the body.[27]

At birth these marks appear pink and with soft consistence, after the course of the years they become progressively darker, in adulthood they acquired nodular and hypertrophic appearance, making them cosmetically troublesome.

Port wine stains treatment follows the maxima of: “The earlier, the better”. Early treatment during childhood when blood vessels are not completely mature exhibit better long-term results, than if they are treated in more advanced phases. Laser treatment has become the standard therapy in this kind of lesions, since the introduction of laser the main option is the PDL. Depending on the they must be adjusted, earlier pinky lesions need more superficial wavelengths while deeper lesions are more beneficiated by deeper wavelengths. The localization of the lesion is also important as frontotemporal lesions respond better than those located in V2 trigeminal innervation which do not present well response to laser therapy. A study was performed with Long-pulsed 532 nm Nd:YAG laser [15], results were safe without appearance of residual marks. Patients with tendency to produce abnormal cicatrisation, those with systemic diseases or immunocompromised were excluded.

14 The procedure included: -Local anaesthesia for children -Cooling pre- and post- boost with cool sapphire -Advice to avoid sun and use of sunscreen As adverse reactions some patients presented transient erythema, scaliness, burning sensation post session. Results were satisfactory >50% of improvement in 50% of patients. PWS treatment is strongly recommended to be as early as possible as this kind of lesions don’t regress with age, the patches become darker, thicker and can acquire nodular appearance.

Also according to the European Guidelines from 2015[10], the use of dual LPDL 595 nm plus 1064 nm Nd:YAG is suggested for resistant or advanced stage lesions as initial treatment choice due its increase penetration, taking into account a higher risk to produce scarring or ulceration, as well as Nd:YAG alone, alexandrite and diode lasers.

The results of a dual wavelength action of PDL and Nd:YAG laser in a retrospective23 study where PDL energy was 6-9 J/cm2 with duration of 0,5-10 milliseconds and Nd:YAG was 10-40 milliseconds with energy fluency of 20-60 J/cm2; this is called pulsed sequential dual wavelength and it was conclude to be an useful first therapeutic tool due to its safety and good cosmetic outcomes.

Telangiectasias are dilatations of small size blood vessels due to the release of vasoactive substances as hormones. They are asymptomatic and cosmetic is one of the main patient’s concerns regarding this pathology. usually appear commonly in the face with predilection for the nasal region and medial tight. They are classified into four main groups: simple/linear, arborizing/spider, papular and punctiform. Laser choice in treatment of telangiectasias depends on localization. Superficial telangiectasis is one of the main focuses of studies and laser efficacy in treating this kind of lesion is remarkable. Treatment methods for teleangiectasia or leg veins overtime have been sclerotherapy, PDL lasers and electrocautery. The limitations of the previously cited methods are that

15 PDL may not offer a proper response of the lesions or can lead to some degree of hypopigmentation as well as it is not useful in the treatment of large vessels. Sclerotherapy can lead to recurrence. Foam sclerotherapy has been used as ¨gold-standard¨ therapy for telangiectasia treatment. Its main adverse effect is hyperpigmentation, matting, and allergy to sclerosants. Foam sclerotherapy is more effective in the treatment of compared to liquid one. Hyperpigmentation is self-limited even though it can last for more than 1 year. The advantage of sclerotherapy is that it is effective to treat feeder veins as well in the same session. Nd:YAG can be useful in case of allergy or needle phobia. According to Parlar et al. [19] study sclerotherapy offers better results than laser therapy but according to a different study the rate of recurrence is much higher. In a study where long-pulsed Nd:YAG was compared with IPL in the treatment of vascular lesions. They demonstrated that 1064 nm long-pulsed was useful for treatment of leg veins due to its deep penetration that permits selective thermolysis. Surface cooling was used to decrease pain and avoid superficial damage. The assessment was 2-blinded clinicians comparing pre- and post- treatment pictures. The values of absorption and scattering of the laser beam are lower in comparison with IPL, this is compensated by an increase in flow, and this characteristic is useful to avoid superficial skin damage. When blood is heated up to 50-54º C it turns into Met- hemoglobin which is a potent chromophore for Nd:YAG. Side effects of laser therapy are pain, collateral damage to surrounding vessels. To avoid scarring its important to avoid double pulsations on the same area, this study also pays attention to safety methods as the use of small spot sizes. Long-pulsated Nd:YAG laser can be used for resistant telangiectasia for example those that appear in the alae nasae and nasal tip, the reason for the lack of response of this kind of vessels compared to other dilated vessels in the face is that usually facial telangiectasia are veins that simply collapse, but in the nasal area vessels this are composed mainly of from the nasal , this offers more resistance to be obliterated than venules worsening the response to treatment and leading to recanalization after a couple weeks postreatment. However long-pulsed Nd:YAG heats up the entire vessels leading to a more satisfactory results.

A study published in 2012[11] showed the clearance in nasal telangiectasia for 12 patients, five men and seven women previously treated by other lasers modalities (pulse

16 dye laser and/or intense pulse light) after only one session the total clearance of the vessels was 78.3%. The number of vessels diameter of 0,1 mm was reduced by 61,1% and that of diameter 0.2-0.3 mm decreased by 92.2%. After the follow-up that lasted for 12 weeks, eleven patients were very satisfied, one patient reported to be just satisfied due to hyperpigmentation after the procedure. The study concluded that large veins are more responsive to treatment than small ones, this correlated with the leg veins. The study is not a randomized controlled study and comparison among other laser modalities was not performed. But it concluded that: “Long-pulsed Nd:YAG laser can be considered as another effective and safe treatment modality for stubborn telangiectasia even on face, if applied cautiously.”

In contrast, some years before in 2008 a pilot study [22] that enrolled 15 patients reported bad results after 1 month follow-up, 10 patients exhibited no improvement, even though immediate results were satisfactory. 5 patients with facial lesions experienced moderate improvement after 1 month, the energy used for this study ranged from 90-120 J/cm2 this might be the cause of the disparity of results compared with other studies were energy setting was around 200 J/cm2. According to the current guidelines [10] the first line treatment for leg veins is sclerotherapy supported by Parlar et al.[19] study. Then depending on leg teleangiectasia diameter preferred modality are, if < 1mm KTP (532 nm), LPDL (595 nm); in the case of larger veins Nd:YAG 1064 nm, as second line it is possible to use Alexandrite or Diode lasers.

Hereditary Hemorrhagic Teleangiectasia also known, as Osler’s disease is an autosomal dominant disorder, represented by a multisystem vascular dysplasia with leads to episodes of repetitive epistaxis and cutaneous eruptive macules, the clinical triad is composed of: -Multiple cutaneous telangiectasias -Positive family history of the disorder -Recurrent epistaxis They appear more commonly in nose mucosa, mouth, tongue, lip, face, fingertips… many patients are bothersome by the presence of and the continuous blood loss, also there is an important emotional impact due to cosmetic aspects.

17 A pilot study was performed with pulse Nd:YAG laser in 4 patients. In this study [17] a cooling contact device was provided. Nd:YAG laser at 1064 nm presents low selectivity for blood vessels and can lead to thermal damage of contiguous blood vessels. The number of sessions require for this procedure was not registered. The wavelength, pulse duration and the fluency vary among the different vessels size, energy ranges between 120-220 J/cm2. After treatment small atrophy and hypopigmentation were noticed.

In conclusion results were satisfactory with a clearance of 90-100% in palms, chin and checks, but treatment in ears and tongue was painful and did not offer good results.

For the treatment of Osler’s disease when lesions are found in mucosa preferred laser method is KTP, in case of any other region Nd:YAG is an effective tool. Other treatment options include cauterization or sclerotherapy but laser therapy is the preferred method.

Hemangiomas are benign tumours, characterized for an abnormal of vessels [28]. They appear during infancy usually in the first weeks of life, infantile hemangiomas present more tendency to occur in female, pre-term newborns and in low- weight births, some studies suggest that may be a contributing factor to the development of these lesions. The prevalence of the disorder ranges from 10-12%. They appear mainly in head and neck but they can also be found at any part of the body.

Infantile hemangioma follows a natural course characterized by a proliferative phase, a plateau period and a slow involution phase. Usually nearly all of them resolve spontaneously by the age of 9 years old, so one of the treatment options is to adopt a wait and see attitude, they require treatment when functionality is disturbed as for example if they are present in the eyelid, or if they are ulcerated.

There is no a gold-standard therapy for the treatment of hemangiomas, cryotherapy may be used if the lesions are small and superficial or if there is any resistant lesion to after laser therapy. Beta-blockers as can be used with good successful rates to control the proliferative phase of infantile hemangiomas but systemic adverse effects as bradycardia or makes this option not suitable for infants under the age of 5 weeks till 5 months.

18 Laser therapy is useful as a safe and effective method that stimulates regression of the lesion with good cosmetic results.

In a restrospective study [26], were 271 Infantile Haemangiomas were treated in 149 infants, was estimate a comparative of the results obtained by dual therapy of PDL and Nd:YAG (187/271 lesions) and PDL alone (84/271 lesions). Moderate to strong improvement was achieved with dual therapy in a 92,4% of the cases. PDL alone might be useful against superficial hemangiomas but it presents a restricted efficacy if the lesions is deeper than 1-2 mm, in these cases the aid of Nd:YAG as an adjuvant device improves the outcomes as it can enter as deep as 10 mm in the skin. Results of this study are supported by similar studies Kjell et al.[25] proved that combination of PDL plus Nd:YAG and short anesthesia is an effective and with low rate of adverse effects treatment method for IH.

In a study carried out with 794 Chinese patients [24] they demonstrate some factor affecting treatment response, according to this study one of the factors that contribute to a better response of the lesion is the age, older ages correlates with a better response. Lesion size did not seem to affect response, but efficacy is worse in deeper, subcutaneous or mixed type lesions. It is important to mention that according the authors of restrospective study proliferative phase of IH cannot be controlled by PDL.

Diagnosis of Infantile Hemangiomas can be confirmed by duplex US and according to most of the articles laser treatment can be continued until satisfactory results have been obtained or duplex US has confirmed a strongly regression of the lesion or non- traceable irrigation is found. Systemic therapy with beta blockers in conjunction with laser therapy optimize the results in the case of proliferative IH. It is important to remember that these lesions are commonly treated in children so local anaesthesia is advisable to used. The recommendations support the conclusions obtained by the publications related to this topic, where PDL is exposed as first line treatment in case of superficial lesions, afterwards Nd:YAG plays its role achieving deeper penetration on skin but in the guidelines there is no contemplation about dual therapy of Nd:YAG plus PDL.

19 Cherry angiomas are the most frequent benign acquired vascular lesions. They have red, papular appearance. They are formed on skin due to an overgrowth of blood vessels, the mechanisms that influence its development are not known yet, but they might be triggered by stress or exposure to irritative substances, there are as well suggestions that indicate that these lesions can be inherited as they are common among family members. Cherry angiomas are small in size, can appear anytime during life, but are more prevalent after 30 years of life. It is not strange to find satellite lesions around a central senile angioma, they are asymptomatic, but can bleed after rupture or repetitive trauma. Cherry angiomas have predilection to appear in the trunk especially in the back but they can appear as other vascular lesions at any part of the body. They can resolve spontaneously.

Methods for elimination of these lesions include shave excision, cryotherapy, electrodessication or laser ablation. Laser ablation presents better cosmetic outcomes.

In a study were KTP laser was compared with Nd:YAG laser[20] results showed that Nd:YAG treatment required less number of sessions with the disadvantage of present higher rate of adverse effect which included pain, erythema and scar formations. One of the most common side effects of Nd:YAG laser include hyperpigmentation, so this study suggest that is better to use this laser modality in darkly pigmented individuals as the risk of pigmentation is lower.

KTP laser has a penetration of 532 nm in comparison with the 1064 nm of Nd:YAG, making this laser more suitable for superficial lesions, as is exposed in Table 1. The target is the oxyhemoglobin, but melanin is also a target this can lead to pigmentation disturbances more commonly hyperpigmentation. Higher number of sessions is required for these lesions. Due to the report of side effects when Nd:YAG is the chosen modality; it is concluded, supported by the results found in this study that KTP is the preferred laser. Nd:YAG can be included as a secondary line option.

20 Angiokeratomas are similar to cherry angiomas, they are benign acquired tumors arising from the , angiokeratomas are hyperkeratotic vascular lesions produced by over distended blood vessels with verrocous, dark red or violaceous appearance. They can be found diffusely across all body they are related to Fabry disease (angiokeratoma corporis diffusum), but the most common presentation is as solitary angiokeratomas, listing the classification we can also find Mibelli, Fordyce or angiokeratoma circumscriptum.

Angiokeratomas treatment options are excision (if they are not large), laser therapy, electrocoagulation or cryotherapy, the last two of them may lead to residual marks or scarring. According guidelines transcutaneous laser therapy can be used in angiokeratomas. There is no many literature relating Nd:YAG laser and angiokeratomas treatments compared with other laser modalities. In this review the treatment of a solitary angiokeratoma is included, the study was performed in 2015[14] and presents the response of a 13 years old age with a lesion in the right upper leg, after the therapy with Nd:YAG laser, 2 sessions were required with 4 weeks interval between them to accomplish the results that concluded that Nd:YAG laser is effective and safe for the treatment of this lesion, no adverse reactions were reported after 3 months follow up. The energy required for this process was 80-130 J/cm2 with long-pulsated Nd:YAG that permits deeper penetration, this is effective for the hyperkeratosis that required the macropulses to offer a satisfactory response.

Pyogenic granuloma, also known as lobular capillary hemangiomas, are solitary exophytic benign tumorations of the skin or mucosa, characterised by rapid growth. Pyogenic granuloma cause is not known, it is believed that hormones, trauma, some or virus may predispose to this kind of lesions as they may alter the angiogenesis growth factors. They are a common tumoration that can be found in head or in extremities, it increases its incidence during especially in oral mucosa [29]. They are small, erythematous sessile papulonodular lesions, that can reach 6,5 mm. Pyogenic granuloma has tendency to bleed after trauma and become ulcerated. Treatment options include surgical excision, electrocautery, cryosurgery and laser therapy, the last option is gaining more and more supporters, among laser options for

21 these kind of lesions we can find Laser CO2, Argon, PDL, Nd:YAG. For a successful treatment outcome is necessary to obliterate the central afferent vessel. In 2012 Stefan H et al. [18] carried out a prospective study were 20 patients were treated with Nd:YAG. Good results were obtained in 19/20 patients were recurrence of the lesion did not occur after the follow-up period. Only one patient presented non- stoppable bleeding and carbon dioxide laser was necessary to stop it. PDL is one of the most used options for pyogenic granuloma especially if they are superficial and are located in difficult access places, but Nd:YAG in contrast offers better results when lesions are large. We can conclude that Nd:YAG laser offers good cosmetic outcomes with low recurrence and it is an important alternative when PDL is ineffective.

7. CONCLUSION

Nd:YAG can be used as a first-line treatment for port wine stains, hemangiomas, venous malformations, agiokeratomas, and large pyogenic granulomas. It can also be used as a secondary line treatment in the case of cherry angiomas were the preferred method is KTP, and teleangiectasias. Adjuvant measures such as cooling of the area, need to be performed, in order to minimize damage and avoid side effects such as scarring. Use of sunscreen may prevent hyperpigmentation of the area. Anaesthesia can be used, as this laser method may be painful in some individuals.

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