[Case Series in Dermatologic Surgery] #3. The Most Effective Method for Surgical Treatment of Earlobe Keloid and Prevention of Its Recurrence

CASE

▶ Patient: a 21-year-old woman

▶ Chief complaint: The patient visited the hospital for hard nodular lumps accompanying pain in bilateral earlobes growing bigger in size (duration: for 1 year).

▶ Past medical history and family history: She had received intralesional injection of triamcinolone for 1 year and pressure therapy for several months at a private clinic.

▶ Skin findings: Hard nodular lumps developed from ear piercing scars in bilateral earlobes (Figure 1).

▶ Diagnosis: Earlobe keloid solely based on clinical findings

▶ Treatment: Intramarginal excision (see Figure 5 below) immediately followed by radiation therapy (see the description below), resulting in full recovery without recurrence so far.

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Figure 1. Hard nodular lumps in bilateral earlobes.

Histology findings: Postoperative histological images and histopathologic findings (see Figure 2).

Figure 2. Histopathological findings of keloids (H & E, A, B, C)

Histopathologic findings of the keloids

1. Inside the scar tissue are thick hyaline collagen fibers, with homogeneous eosinophilic staining, proliferated disorderly and widely in bundle (A and B) compared to relatively normal collagens in the lower part (A and C).

2. Proliferation of skin fibroblasts and mucopolysaccharides, especially chondroitin-4-sulfate, is identified between collagen fibers.

3. The blood vessels are decreased unlike in hypertrophic scar or normal tissue recovered after injury.



Histopathologic findings of the keloids

1. Basic knowledge for earlobe surgery

• Skin in front of the ear: The skin is thin and directly attached to the cartilage without adipose layer.

• Local anesthetic injection induces a lot of pain. Tissue dissection and primary skin suture are difficult to perform.

• Skin behind the ear: Relatively thick and loosely attached to the lower cartilage.

• Cartilage: One cartilage shapes the ear. Cartilage injury should be monitored at all times because cartilage infection may develop to fulminant necrotic cartilage in rare cases.

• Auricular region: Wedge resection is available to approximately 1/4 of all, with tie-over dressing that passes through the cartilage.

• Occlusive treatment: Dressing should be removed within 3-4 days due to the risk of Pseudomonas aeruginosa infection, and complete occlusive treatment is contraindicated.

• When a large area of the soft tissue on top of the cartilage has been removed, making it hard to perform primary suture or to expect the formation of granulation tissue by secondary suture, the cartilage should be resected by punch (1.5-2mm) to induce granulation tissue from the soft tissue on the opposite side, or the punching should be immediately followed by skin graft directly to the defect.

• Find the anatomical structures of the ear and their names in the diagram below(Figure 3).

- Helix, Antehelix, Scaphoid Fossa, Triangular Fossa, Crus of Helix, Tragus, Antitragus, Concha, Symba.

 

Figure 3. Diagram.

2. Things to be considered before surgical treatment of earlobe keloids

1) Conventional local treatments include intralesional injection of steroid, bleomycin or 5-FU, silicone gel application or silicone pressure sheet, metal pressure earring such as magnets or splint and cryotherapy, which have limited effect on preventing recurrence.

2) Simple excision followed by pressure has been reported as successful in some cases, although there are few reports on long-term follow-up results. Simple surgical removal is not currently recommended due to high risks of recurrence and exacerbation, but intralesional resection (core, subtotal or intramarginal excision) entails less recurrence.

3) Perioperative steroid injection and postoperative imiquimod application have been attempted to prevent postoperative recurrence, although these methods are not recognized as effective methods due to weak prevention effect.

4) Radiation therapy was found as the most effective method in comparative studies on various treatments.

5) Uncontrolled cases by conventional treatments or recurrent cases after surgery require radiation therapy and should be transferred to a hospital that provides one.

6) Radiation therapy is most effective and successful when performed 3 times consecutively (low-dose fractionated radiotherapy: 12Gy in three fractions) within 24 hours after surgery.

3. Surgical techniques for treatment of keloids

1) Intra-marginal or Subtotal Excision.

Figure 4. Intra-marginal Excision. JAAD 2002;47:307~9.

2) Core Excision with Supra-keloidal Flap.

Figure 5. Core Excision with Supra-keloidal Flap.

3) Preop TRA + Core Excision + RT.

4) My Current Approach: Summary.

4-6 weeks before surgery: Intralesional triamcinolone injection 20mg/ml/2 weeks.

Surgery: core excision with suprakelidal flap under local anesthesia

Radiation therapy within 2 hours after surgery: fractionated RT(12Gy in three fractions).

Figure 6. Preop TRA + Core Excision + RT.

References

1. Dinh Q, Veness M, Richards S. Role of adjuvant radiotherapy in recurrent earlobe keloids. Australas J Dermatol. 2004 Aug;45(3):162~6. Review.

2. Sclafani AP, Gordon L, Chadha M, Romo T 3rd. Prevention of earlobe keloid recurrence with postoperative corticosteroid injections versus radiation therapy: a randomized, prospective study and review of the literature. Dermatol Surg. 1996 Jun;22(6):569~74.

3. Field LM. Subtotal keloid excision--a preferable preventative regarding recurrence. Dermatol Surg. 2001 Mar;27(3):323~4.

4. Lee Y, Minn KW, Baek RM, Hong JJ (2001) A new surgical treatment of keloid: Keloid core excision. Ann Plast Surg 46:135–140.

5. Brian B. Adams, Hugh M. Gloster. Surgical Pearl: Excision with suprakeloidal flap and radiation therapy for keloids. J Am Acad Dermatol 2002;47:307-9.

6. Berman B, Villa A. Imiquimod 5% cream for keloid management’ Dermatol Surg. 2003 Oct;29(10):1050~1.

- To be countinued -

▶ Previous Artlcle : #2. Pigmented Basal Cell Carcinoma on the Face Mimicking a Nevus

[Regenerative Surgery] #3. Acellular Dermal Matrix

 

Acellular dermal matrix, developed in the form of sheet, has been used for various regeneration and reconstruction purposes, such as for burn, injury and ulcer, abdominal wall reconstruction, breasts reconstruction, vocal cord paralysis surgery and interdental papilla graft. Acellular dermal matrix is also called a ‘dermal regeneration template’ since it maintains 3-dimentional structure of the dermis, playing the role as a scaffold of various cells and stem cells.



With the development of emergency medicine since the 1970s, the survival rate of patients with extensive burns has increased, leading to the development of artificial skins for such patients. The shortage of dermis was the cause of severe scar and contracture, giving rise to the necessity of regenerating important structural and physical properties of the dermis and, as a result, the development of dermal regeneration template (acellular dermal matrix). The coverage of dermal regeneration template spans from the treatment of extensive burns to improvement of burn scars, correction of contracture, and the treatments of exposed bones, tendons, joints, and acute or chronic wounds; the indication is still in the progress of expanding. In other words, acellular dermal matrix has become an important tool and element for regenerative surgery.

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The skin is roughly composed of the epidermal tissues in the body surface and the dermis below. The main roles of the epidermis are to prevent water loss inside the body and to protect the body from foreign hazardous materials, such as bacteria and ultraviolet. The outermost multiple layers of stratum corneum, cells producing pigments and blocking ultraviolet, Langerhans cells eliciting immune function, hair cells that forms the hair, and skin appendages including sweat glands are all located in the epidermis. Basal cells, located at the bottom of the epidermis, do not have any special protective function but is the mother of various types of cells that have protective function. Small wound in the skin can heal because these basal cells make new cells constantly. The dermis under the epidermis is composed of fibrotic proteins (collagen) and fibroblasts tangled in places like threads. Since capillaries can reach up to the dermis, nutrition and various growth factors are supplied to the epidermal cells by diffusion.



Stem cells are cells that have the potential to differentiate repeatedly, with the abilities to replicate themselves and to differentiate to various tissues. Stem cells are found abundantly in an embryo after a few days of fertilization. Stem cells can be obtained, therefore, from surplus embryos produced for fertility treatment or from embryos replication without fertilization. Human muscle cells or skin cells may be obtained from these stem cells under an appropriate condition. Because of the self-replicating ability, stem cells can be mass cultured and differentiated to skin cells to obtain large amount of artificial skin.



Early artificial skin studies mainly focused on attaching temporary protective film, such as silicone or dressing, or transplanting autologous skin graft, to provide a temporary protection until new skin grows. Recent studies focus on the technology of replacing human tissues, damaged by disease, injury or aging, with cultured tissue cells to minimize rejection reaction by means of tissue engineering.



An adult patient with severe skin damage generally requires 2,000-4,000 cm² of skin graft; especially those with extensive burns require bioartificial skin proliferated tens or hundreds of times from small skin tissue. Artificial skin is a material that regenerates damaged skin, and may be divided to wound dressing, artificial dermis (acellular dermal matrix), bioartificial skin (cultured skin) depending on the roles.



1) Wound Dressing

Once a wound occurs, it is important to recover the skin structure similar to the original state. A wound, if left open for a long period of time, may accompany primary complications, such as infection, and may cause pain during the treatment period and discomfort in daily life; therefore, the wound should be closed in the early phase. In the past, it was common to attempt passive treatments, such as applying disinfectant and covering with gauze until the wound is closed. Attaching a temporary protection, such as silicone or dressing, or transplanting autologous skin graft until new skin grows, have been the most common method of temporary wound protection for burns or traumas from the early days of artificial skin study until now. Wound dressing is useful for preventing water leak from inside the body, absorbing exudate (fluid that filters from the blood vessels into lesions, in the presence of inflammation), and preventing bacterial invasion from the outside and infection. Other than gels, dressings are made of porous membrane, using polyurethane membrane or chitin, or freeze-dried pig leather.



2) Artificial Dermis (Acellular Dermal Matrix)

Artificial skin is used for wounds with skin defect due to extensive burns or surgery, and is made of synthetic or natural polymers. The upper layer is made of silicone to prevent the loss of body fluid by vaporization, and the lower layer is made of collagen, to induce angiogenesis and regeneration of connective tissues, actively helping regeneration to the original skin tissues and providing an easy passage for body cells after being disintegrated and absorbed in the body. It is hard to expect natural healing process by conservative treatment when a skin defect is very wide due to deep burns or skin cancer resection. Such cases are commonly reconstructed by skin graft or flap operation; recently, various types of dermis are available for transplantation, allowing much easier and simple covering and both functionally and aesthetically superior results. Transplantation with artificially synthesized dermal tissue may prevent severe scar and scar contracture that may happen after skin restoration to some extent. Although there might be some difference between products, artificial dermis is composed of collagens, glycoproteins and elastic fibers, which are constituents of the dermis, preventing scar formation, inducing dermal synthesis, and protecting from scar contracture. Artificial dermis is highly porous and is structured for provide a high penetration power. Structural determinants of regeneration ability in each artificial dermis are chemical constituents, size and rate of stoma, and the degeneration rate of the artificial dermis. Integra (Lifesciences, Plainsboro, NJ, USA), Pelnac (Gunze, Tokyo, Japan), Terudermis (Olympus Terumo, Tokyo, Japan), and Matriderm (Skin Health, Billerbeck, Germany) are the commonly used products in Korea.

Allogenic dermis can be classified separately from artificial dermis. Allogenic dermis is an acellular dermal matrix made from human skin by removing immunoreactive epidermal and dermal cells and then glycerol-preserved or cryopreserved, with basic 3-dimensional structure preserved in the state most similar to the actual skin. Alloderm (LifeCell, Branchburg, NJ, USA), developed in the US, is currently being imported in the Korea market. Surederm (Hans Biomed, Daejeon, Korea) and CGCryoDerm (CG Bio, Seongnam, Korea), developed in Korea, is also widely used. Dermal substitutes had been commonly used for the treatment of severe burns, but are currently being used for wound dressing and implantation in various fields, including burn, reconstructive plastic surgery, abdominal wall reconstruction and breast reconstruction.



For your information, autogenous dermal graft is an aesthetically superior skin grafting method to overcome disadvantages of conventional skin grafting. This method grafts the dermal layer only and induces epithelialization from the surrounding tissues of the recipient site to minimize hypertrophic scar in the donor site and color difference in the recipient site. The melanocytes contained in the epithelium are distributed throughout the body with different density and activity per each area, affecting the skin color. Skin graft for a wound may have different color from the surrounding tissues, therefore. Such color difference may be reduced by grafting the dermal layer only and then letting the epithelium regenerate secondarily from the epithelium of the surrounding tissues. The donor site scar can be also minimized in this manner, because the donor site can be covered again by the remaining epithelium in place. However, it takes a longer time until the epithelium is regenerated if the skin defect is large.



3) Bioartificial Skin (Cultured Skin)

Bioartificial skin may be used for extensive burns, skin ulcer due to diabetes mellitus, or skin damages. For this method, collected and cultured skin cells are attached to artificial skin to form tissues. Bioartificial skin rarely causes rejection reaction and the skin size can be modified as much as needed, even for severe burns. Because it is made from biocompatible materials according to the desired structure and function by 3-dimentional skin cell culture, bioartificial skin is a living artificial skin, almost similar to the actual skin. Among the representative products is Holoderm (TEGO Science), a cultured epidermal autograft, obtained by culturing small amount of skin (1-3 cm²) collected from the patient.



As discussed earlier, artificial dermis (acellular dermal matrix) is made by removing all cellular components, except for tissue function and structure, from collected cells, combining collagen by enzyme to strengthen the structure, and sterilizing the tissue to reduce the risk of infection before being distributed. Extracellular matrix is one of the main components of the dermis and plays an important role in the process of tissue recovery. The main constituents are hyaluronic acid, proteoglycan and collagen, and artificial dermis can replace normal extracellular matrix. Artificial dermis is normally processed from human or animal but may also be made from synthetic materials. In conclusion, artificial dermis was developed for the treatment of extensive burns and has been used as one of important strategies for reducing donor site morbidity by simpler skin graft, not flap operation, to treat and recover exacerbated inflammation of a chronic wound, such as diabetic foot, or wounds with exposed ligaments or bones. The indications for artificial dermis has rapidly expanded to be used as a scaffold for implants in breast reconstruction surgeries, for shaping in plastic surgeries, or for increasing volume in reconstruction surgeries for congenital malformations, trauma or cancer.

- To be continued -

▶ Previous Artlcle : #2. Elements of Tissue Regeneration

[The Principle and Application of Laser(with focus on medical lasers)] #3. Lasers and Soft Tissue Interaction Ⅰ

5-1. Optical process of energy transfer

Since the development of laser in 1960, it had not been used a lot for medical use as now for about 25 years due to the lack of fundamental understanding on the process of interaction between laser and soft tissue until mid-1980s. It was from 2000s when the subject had rapidly gained attention with more and more studies being published, and now laser has become the basic tool for surgery. Understanding the process would be of much help for appropriate use of medical laser. In order to understand the interaction of laser with soft tissue, it is most important to know what optical process occurs when the skin is irradiated by the laser light. Skin tissues exposed to light undergoes the following 4 optical processes:

1) Absorption

2) Scattering

3) Transmission

4) Reflection

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There are various forms of energy in the nature with different sizes determined by the physical condition. Thermal energy, chemical energy, sound energy, light energy and kinetic energy are the examples.

Among these, laser is a form of light energy which shifts its form when interacting with another material. What is common between medical and industrial lasers is the change in the form of energy by absorption. For example, when welding or cutting a steel plate with laser, the laser is absorbed to the steel plate in the form of light energy and then changes to thermal energy, melting the steel plate for welding or cutting. Likewise, for the treatment of vascular lesions in the face or legs, laser absorbed in the form of light energy should be changed to thermal energy for coagulation or contraction of blood vessels. Thus, without absorption, no physical process can occur. Given the importance of absorption, unfortunately, human skin absorbs different amount of laser depending on the wavelength, causing the hassle of having to choose the laser which emits a wavelength that absorbs well in the lesion to be treated. Figure 1 shows optical absorption coefficients of light-absorbing chromophores. The representative soft tissue components are protein, melanin, hemoglobin, water and collagen.

Figure 1. Optical absorption coefficients of principal tissue chromophores in the 0.1-12 um spectral region.

Absorption means light energy transferring to another form of energy when the light interacts with molecules or atoms. It is difficult to describe accurately the process of which the light is absorbed in the tissue due to the non-uniform and complex structure of skin tissue. This will be described later conceptually with a simple formula.

Scattering refers to the physical process where light is deviated from a straight trajectory by collision with molecules, atoms or particles smaller than the wavelength of light. Scattering occurs in a gas, liquid and solid, although the scattered light more frequently appear as refraction or reflection of light in a solid or liquid. Scattered light appears inside an object (such as in the skin tissue) only when the skin tissue has irregular density or orientation of the arranged molecules. For example, when irradiating a laser light in the visible spectrum to very non-uniform skin tissues, the area near the irradiated site appears bright due to backscatter phenomenon of light. As skin tissues cause much scattering effect to light, the laser light has limited penetration depth without proceeding deeper into the skin. Since the penetration depth also varies depending on the wavelength of light, the wavelength should be selected properly according to the depth of the lesion to be treated. The fluence irradiated on the skin should be increased to obtain a satisfactory therapeutic effect because the fluence per unit area decreases as scattering increases. The penetration depth in the skin becomes greater from visible light to infrared light until reaching the plateau with Nd:YAG laser wavelength (1064nm), after which the depth decreases again.

Transmission is a very important physical property for selective treatment. For example, Q-switched Nd:YAG laser (1064nm wavelength), which is used for pigmented lesions located deep in the dermis layer, is not therapeutic if it is absorbed in the epidermis layer and does not reach the dermis layer. The Q-switched Nd:YAG laser (1064nm wavelength) can be therapeutic because the absorption rate is smaller than the transmission rate in the epidermis layer, while the transmission rate is smaller than the absorption rate in the dermis layer. As every material on earth (including skin tissue) has its own absorption spectrum, selective treatment is available without inflicting damage to the other tissues if only the exact absorption spectrum can be found. This is the unique property of laser light.

Reflection is a physical property that has no interaction with a laser light and has no effect on a therapy. For example, hard tissues, such as enamel, reflect all laser lights from the surface, making it difficult to treat. However, enamel can be treated as well when Er:YAG laser (2940nm) is used with water. This is because the water on the surface becomes rapidly hot by absorbing laser light and then explodes, ablating the enamel layer.

The above-described 4 optical phenomena, absorption in relation to the wavelength of light and energy, scattering in relation to the light penetration depth and fluence, and transmission in relation to selective treatment, should be well understood for better use of medical laser. The links among these properties should be also well understood because they occur simultaneously when irradiating a laser to skin tissues.

5-2. Parameters of lasers

Among the methods of laser oscillation are continuous wave oscillation and pulse oscillation. Most of the current medical lasers adopt the pulse oscillation to minimize thermal damage to surrounding normal tissues. The following parameters are for pulse lasers:

1) Energy

2) Power (P)

3) Beam profile/pattern

4) Pulse duration

These 4 parameters should be considered first when evaluating lasers of the same wavelength.

Energy means the capability of work, or energy transfer between two objects (that is, laser energy delivering energy to skin tissues), and is presented as Joule [J]. The fluence mentioned above when describing scattering refers to energy per unit area [J/cm²]. For example, if output energy is 1 Joule and the diameter of the output beam is 4mm, the area of the output beam is 3.14x0.2x0.2cm², or approximately 0.13 cm², and the resulting fluence is 1/0.13=7.7J/cm². High fluence or energy means greater ability to deliver energy to the skin tissue, or even therapeutic injury of the epithelia beyond certain level of fluence or energy. Therefore, the epithelia should be cooled down properly to minimize thermal injury during a procedure.

Power/P means the amount of work per unit time, or the change of energy per unit time (P=Joule/time), and is presented as W[watt]. Power is represented by average power and peak power. The average power is energy [J] x pulse repletion rates [Hz], while the peak power is energy [J] / pulse duration [s]. For example, when pulse duration is 5ns (5x10^-9s), maximum pulse repetition rate is 10Hz and output energy is 1 Joule, the average power is 10W and the peak power is 2x10⁸ W (200MW).

Beam profile is determined by the structure of the laser resonator and there are roughly two types. One is the output from multimode resonator and the other is the output from single-mode resonator. Typically, the laser from single-mode has a bell-shaped Gaussian profile, while the laser from multimode has non-uniform beam profile. It is the dream of laser researchers to design and develop a resonator for flat-top beam profile, which is theoretically impossible. In case of Q-switched high power solid-state laser, the great thermal lens effect of the gain medium – Nd:YAG crystal, for example – makes it impossible to realize flat-top beam profile. Nevertheless, unstable resonator or a resonator which can compensate for the thermal lens effect inside the resonator can be used to produce relatively uniform laser, and these suggestions are often being used in practice.

Pulse duration is the time it takes to generate laser beam. The full width at half maximum on the axis of time is expressed as pulse duration. Lasers can be categorized to long pulse (>1ms), free-running (~tens or hundreds ns), short-pulse (~ns) or ultra-short –pulse (<1ns) depending on the pulse duration. In general, long pulse lasers are used for maximized thermal effect, while short pulse (Q-switched) lasers are used for minimized thermal effect with high peak power.

- To be continued -

▶ Previous Artlcle : #2. Development Process and Types of Lasers

[History and Development of Cutaneous Lasers ] #3. Development of Vascular Laser Ⅱ-1

Continuing from the last chapter, the development of vascular lasers for treating nevus flammeus will be discussed this time. In order to understand why nevus flammeus has been brought up as a topic in the history, it is necessary to understand the disease itself. Nevus flammeus, or Port-wine stain, is a congenital disease not classified as a hemangioma, and is the most common type of capillary malformation. The term had been dismissed as a 19^th century’s word in dermatology textbooks, but is now one of the most commonly found terms in articles with the development of vascular lasers.

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Nevus Flammeus (Port-wine Stain)

Being the most common type of capillary malformation, nevus flammeus appears in various sizes; it may develop on any area with geographical shape or along the dermatome. The lesion appears as light pink at first, turns to dark red throughout the adolescence, and to purple in the middle age. The surface becomes uneven; sometimes  nodules develop with aging. Histological finding is dilated ecstatic vessels composed of flat endothelial cells at the papillary dermis or the upper part of reticular dermis.



Various treatments, including electrocautery, tattoo, dermabrasion and cryotherapy, had been attempted since long before, but they left scar and were not effective. Some textbooks even recommended a makeup to cover the lesion with a covermark. In my personal experience, nevus flammeus is not detectable in most newborn infants and a light pink spot starts to appear in 1-2 weeks after birth. The thickness of the blood vessel becomes thicker with age. Nevus flammeus is difficult to treat with a laser without general anesthesia or conscious sedation in 6 months to 1 year after birth. Therefore, the importance of treating exposed nevus flammeus with a proper laser upon detection after birth cannot be stressed enough. It would be hard for a clinician without an experience of treating infants to imagine the importance of transferring infants with early nevus flammeus detected at a Pediatrics or Obstetrics and Gynecology department to a hospital equipped with a suitable therapeutic facility.



However, it is possible only when the clinician is aware of a hospital that is equipped with proper lasers and sometimes even the facility for general anesthesia (since it is difficult to equip both laser devices and general anesthesia facilities in the same operation room, even teaching hospitals are rarely prepared with such luxury). This is the matter of a child’s lifetime and I urge more attention to this matter from clinicians reading this article. Ultimately, nevus flammeus is the aggregation of dilated blood vessels, each vessel situated close to each other; therefore, the lesion is highly likely to end up with a scar if the blood vessels are not damaged selectively. Sporadic telangiectasia distributed here and there can be eliminated by a CO₂ laser or eletrocautery. Thick blood vessels may require a laser therapy relatively less because they might be treated with a sclerotherapy. Probably this is why lasers that affect the blood vessels selectively have been first applied to nevus flammeus.



Nevus flammeus could not be treated properly due to the issue of scarring; however, the treatment of nevus flammeus has took a new turn since starting to use argon lasers for the lesion. Argon laser would inflict damages to the surrounding tissues at a high rate, the issue of scarring is still remaining although this side effect has been remarkably reduced. However, 577nm pulsed dye laser, which had started to be used experimentally between the late 1970s and the early 1980s, had a physical property that could minimize the injury to the surrounding tissues, a development which could be considered as a whole new therapy. The development of dye lasers partially overlapped with the use of argon laser in time, often being presented as reversed order of dates for article publication. However, in this article, I would like to discuss the development of vascular lasers for nevus flammeus by introducing main papers. The order may not match with the sequence of publication, possibly because of some difference in the time of publication and the process of theoretical or practical therapeutic development.



Finally, you should keep in mind, when reading the following studies, that nevus flammeus in infants or children was the main target when the concept of selective photothermolysis was first studied and published. Nevus flammeus in adults accompanies thicker blood vessels and changes of the surrounding tissues unlike that in children. If you are not aware of this difference, you may not be able to understand the treatment of nevus inflammeus or vascular lasers.



1. Port-wine Stains, Nevus Flammeus

The nature and evolution of port-wine stains: a computer-assisted study. Barsky SH, Rosen S, Geer DE, Noe JM. J Invest Dermatol. 1980 Mar;74(3):154~7.

Nevus fllameus is characterized by increased number of blood vessels and ectasia. The number of blood vessels is the greatest immediately under the epidermis and gradually decreases toward the bottom. Mean depth is 0.46±0.17mm. The diameters of blood vessels become larger, and the color turns from pink to purple, with aging. Blood vessels have comparable characteristics at each depth until reaching 0.8mm – that is, blood vessels in each depth have unexpectedly uniform thickness.



2. Nevus Flammeus Treatment Using Unselective Lasers, including Argon Laser and Copper Vapor Laser

Hypertrophic scarring in argon Laser treatment of port-wine stains. Dixon JA, Huether S, Rotering R. Plast Reconstr Surg. 1984 May;73(5):771~9.

Argon laser at 488nm and 514nm is not for selective absorption in the blood vessel nor is it suitable for the concept of selective photothermolysis due to the pulse duration longer than the thermal relaxation time of the blood vessels comprising a nevus flammeus. It had been introduced for clinical use, however, because it was more effective than other previous treatments. This laser could not avoid inflicting damage to normal tissues, contributing to high frequency of scarring, which was as high as 38% among patients younger than 12 years old and 21% in older patients in the Group 1. In the Group 2, 13.7% experienced scarring. The higher frequency of scarring in the children suggests the following: children, who have thinner blood vessel in the nevus flammeus, require a laser with relatively shorter pulse duration for selective damage, which was not the case in argon laser. This suggests, however, that argon laser would be worthwhile in adult hypertrophic type with thick blood vessels.  Yet, argon lasers are practically not used in hospitals anymore. Considering what would be the most appropriate laser for a certain patient among all kinds of lasers made by mankind, it is regrettable that argon laser has disappearred already.



Histologic responses of port-wine stains treated by Argon, Carbon Dioxide, and tunable Dye Lasers. A preliminary report. Tan OT, Carney JM, Margolis R, Seki Y, Boll J, Anderson RR, Parrish JA. Arch Dermatol. 1986 Sep; 122(9):1016~22.

It is predictable that tunable Dye Laser would cause less epidermal damage and fibrosis, and thereby less clinical side effects, compared to argon laser or CO₂ laser based on the histological findings. This would appear simple now but please keep in mind that this study was performed when argon laser was commonly used, when scarring was considered as an inevitable result, not a side effect, before Dye Laser is commonly used.



Histological responses of port-wine stains in brown skin after 578nm Copper Vapor Laser treatment. Chung JH, Koh WS, Youn JI. Lasers Surg Med. 1996;18(4):358~66.

I personally performed the histology and staining in this study. It was a study that fell behind considering that it was published when Dye Laser was used already, which is why this study is introduced here before its actual time of publication. 578nm Copper Vapor Laser satisfies selective photothermolysis quite well for damaging blood vessels considering the wavelength, but 30-200ms pulse duration is not suitable for selective damaging of blood vessels of nevus flammeus. Nonetheless, the selective wavelength for HbO2 resulted in histological findings of selective blood vessel damage under some conditions, unlike argon laser. Higher fluence or longer pulse duration was associated with easy epidermal damage, however. Furthermore, the depth of blood vessel damage was only as low as 0.4mm because 577nm or 578nm does not provide enough penetration depth as well.



3.The Beginning of the Concept of Selective Photothermolysis and Application for the Treatment of Nevus Flammeus; Introduction of Flash Lamp pumped tunable Pulsed Dye Laser

Microvasculature can be selectively damaged using dye lasers: a basic theory and experimental evidence in human skin. Anderson RR, Parrish JA. Lasers Surg Med. 1981;1(3):263~76.

This study proved selective microvessel damage by irradiating flashlamp pumped Dye Laser (0.3 microsecond) at 577nm, which is the absorption band of HbO₂, to average Caucasians.  Argon laser required 20J/cm²(514 and 488 nm, approximately 100msec) and inflicted injury to areas other than blood vessels, but this was the first study to show that 577nm Pulsed Dye Laser could damage blood vessels selectively with approximately 2J/cm². At this time, argon laser was being used, but this study might have been initiated to overcome the frequent scarring of argon laser. Since this was a study targeted on microvessels of in normal skin, the blood vessels were very superficial and thin (expected TRT approximately 1ms). The flashlamp pumped Dye Laser was easily applied to port-wine stains comprised of blood vessels with capillary malformation but relatively thinner than other hemangiomas or telangiectasia, which is why other studies from the same authors focused on the treatment of nevus flammeus. It is worth noting that the pulse duration was very short. This study is meaningful in that it marked the starting point of a long history of Dye Laser in the future, such as longer wavelength and longer pulse duration. Rox Anderson later published a study explaining the concept of selective photothermolysis in the Science based on Dye Laser used in this study.



Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Anderson RR, Parrish JA. Science. 1983 Apr 29;220(4596):524~7.

This study used the term ‘selective photothermolysis’ for the first time and used the same laser as that used in the above study (Candela Model SLL-1100, 577nm, 0.3 microsecond). The authors selected 577nm, which can penetrate most deeply among the absorption peaks of HbO₂, which are 418, 542 and 577 nm. Thermal relaxation time for 20um blood vessel was hypothesized as 50 microseconds, and 0.3 microseconds was found to damage blood vessels without damaging the surrounding tissues or the epidermis. What’s worth noting in this study is that the thickness of the target blood vessel was as thin as 20um, and that purpura occurred. This thickness is similar to or slightly thinner than the blood vessels of nevus flammeus in newborn infants.

- To be continued-

▶ Previous Artlcle : #2. Development of Vascular Laser I