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Chapter
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13
A
Treatment of Leg Telangiectasias with Laser and High-Intensity Pulsed Light
D E
Figure 13.40 Treatment of telangiectatic matting (TM) 7 months after sclerotherapy (SCL) treatment of telangiectasia on the medial knee. A, Immediately
before initial SCL treatment. B, Development of persistent TM 7 months after initial treatment. C, 3 months after flashlamp-pumped pulsed dye laser (PDL)
and PDL/SCL treatment, showing the development of a persistent superficial ulceration in the two PDL/SCL treatment sites. Anterior site treated with PDL
at 7 J/cm2, 31 pulses, before SCL with polidocanol (POL) 0.5%, 1 mL; medial site treated with PDL alone at 7 J/cm2, 27 pulses; posterior site treated with
PDL at 7 J/cm2, 31 pulses, before SCL with POL 0.75, 1 mL. D, 7 months after initial PDL and PDL/SCL treatment, showing persistent TM and healing of the
ulceration. E,
6 months after treatment with chromated glycerin solution (diluted 1 : 1 with lidocaine 1%), 2 mL. Resolution of the TM has occurred.
B
C
pyogenic granuloma by combining the 1,064-nm laser with
glycerin sclerotherapy. A series of three sessions, spaced 2 to
3 weeks apart, were administered. The spot size was varied
over subsequent visits to parallel the decreasing size of the
lesion; fluences varied between 200 to 360 J/cm2, and the
pulse width was kept constant at 40 ms. Immediately after
the laser treatment, the patient underwent an intralesional
injection with 0.1 to 0.2 mL of compounded glycerin (14.5 mL
of glycerin, 6 mL of bacteriostatic water, and 9.5 mL of lidocaine 1% with epinephrine (adrenaline)). The lesion, which
was located on the patient’s lip, resolved completely and an
excellent cosmetic outcome remained at a 2-year follow-up
visit. This case is pertinent as, although the combined laser
and sclerosant treatment was not administered to leg telangiectasias, it was used to treat a thick and deep vascular lesion
that necessitated a longer wavelength device. Theoretically,
this technique could be used to treat leg telangiectasias of the
364
deeper, larger variety. However, given the potential for scarring
associated with the 1064-nm Nd:YAG laser, the super iority of
sclerotherapy alone in many cases, and the potential for synergistic adverse effects when lasers are used in combination
with sclerotherapy, the authors do not routinely advise combining these two modalities to treat leg telangiectasias.
Conclusions
Since sclerotherapy treatment is relatively cost-effective compared to laser or IPL treatment, when is it appropriate to use
this advanced therapy? Obviously, needle-phobic patients
will tolerate this technology even though the pain from lasers
and IPL is more intense than that of sclerotherapy with all
but hypertonic solutions. Patients who are prone to TM are
also appropriate candidates. Vessels below the ankle are
particularly appropriate to treat with lasers and light, since
https://t.me/med1917
sclerotherapy has a relatively high incidence of ulceration in
this area due to the higher distribution of arteriovenous anastomosis (see Chapter 8). Finally, patients who have vessels
that are resistant to sclerotherapy are excellent candidates.
Efficacy of 75% clearance with two to three IPL treatments has
been reported in sclerotherapy-resistant vessels.
118
In a similar ‘vein’, enhanced efficacy of treatment may
occur by combining sclerotherapy with lasers or IPL. This
technique is not new and was even reported approximately 30
years ago by the Italian vascular surgeon Leonardo Corcos,
who used the argon laser to spot-weld telangiectasia so
the sclerosing solution could have prolonged contact with
the vessel wall.
25
This combination technique also gives the
patient the opportunity to experience ‘laser’ treatment, which
is perceived as more advanced than merely injecting a solution
into a vein.
The optimal efficacy in treating common leg telangiectasia
uses sclerotherapy to treat the feeding venous system and a
laser or IPL to seal superficial vessels, thus preventing extravasation with resulting pigmentation, recanalization, and TM.
So, is there a single laser that can adequately treat leg veins?
The answer is yes and no. Yes, lasers are now available with
pulse durations optimized to treat blood vessels of various
sizes. One can select virtually any wavelength from 532 nm
through to 1064 nm, as well as a broad spectrum of IPL. It
has been demonstrated that any wavelength can be used effectively as long as the pulse duration matches the diameter of
the vessel and an appropriate fluence is utilized. This also
assumes that the epidermis will be protected from nonspecific
thermal effects by a variety of cooling and pulsing scenarios.
One can cool the skin directly with a contact probe before and
after the laser pulse or through a sapphire window before,
during, and after the laser pulse. Cooling can also be given
dynamically with a cryogen spray before, during, or after the
laser pulse. Most patients prefer dynamic cooling as providing
the highest degree of pain control. Contact cooling is unpredictable in adequately cooling the epidermis; unless optimal
techniques are used, epidermal burns will occur.
However, the answer is also no, as presently available lasers
still require skillful use for safe and effective treatment. The
laser of the future was detailed in a September 2001 publica-
119
tion.
This ideal laser will have a built-in thermal sensor to
detect both epidermal and vascular heating, thus enabling it
to automatically regulate the fluence so that the vessel is completely thermocoagulated, while cooling the epidermis to
maintain its temperature at that of one below a damaging
threshold. Even better would be an infrared sensor that would
determine the location of feeding dermal vessels so that they
too can be treated along with the visible telangiectasia. One
could imagine in the future, the patient placing the leg into a
laser machine that would map the visible veins to be thermocoagulated and automatically treat the entire superficial
venous network. At this time, the only barrier preventing the
development of such a laser is money and the willingness of
a company to produce a machine of this type.
References
References
1. Ross V, Anderson RR. Laser-tissue
interactions. In: Goldman MP, editor.
Cosmetic cutaneous laser surgery.
New York: Elsevier; 2006.
2. Goldman MP. Laser treatment of
cutaneous vascular lesions. In:
Goldman MP, editor. Cosmetic
cutaneous laser surgery. New York;
Elsevier; 2006.
3. Dover JS, Sadick NS, Goldman MP.
The role of lasers and light sources in
the treatment of leg veins. Dermatol
Surg 1999;25:328.
4. Anderson AR, Parrish JA. The optics
of human skin. J Invest Dermatol
1981;77:13.
5. Ross EV, Domankevitz Y. Laser
treatment of leg veins: physical
mechanisms and theoretical
considerations. Lasers Surg Med
2005;36:105.
6. Kunishige JH, Goldberg LH, Friedman
PM. Laser therapy for leg veins.
Clinics Dermatol 2007;25:454.
7. Weiss RA, Weiss MA. Resolution of
pain associated with varicose and
telangiectatic leg veins after
compression sclerotherapy. J Dermatol
Surg Oncol 1990;16:333.
8. Bernstein EF. Clinical characteristics of
500 consecutive patients presenting
for removal of lower extremity spider
veins. Dermatol Surg 2001;27:31.
9. Goldman MP, Kaplan RP, Duffy DM.
Postsclerotherapy hyperpigmentation:
a histologic evaluation. J Dermatol
Surg Oncol 1987;13:547.
10. Duffy DM. Small vessel sclerotherapy:
an overview. In: Callen JP, Dahl MV,
Golitz LE, et al, editors. Advances in
dermatology. Chicago: Year Book
Medical Publishers; 1988.
11. Faria JL de, Moraes IN.
Histopathology of the telangiectasias
associated with varicose veins.
Dermatologia 1963;127:321.
12. Goldman MP. Laser and sclerotherapy
treatment of leg veins: my perspective
on treatment outcomes. Dermatol
Surg 2002;28:969.
13. Braverman IM. Ultrastructure and
organization of the cutaneous
microvasculature in normal and
pathologic states. J Invest Dermatol
1989;93(Suppl):2S.
14. Wokalek H, Vanscheidt W, Martay K,
Leder O. Morphology and localization
of sunburst varicosities: an electron
microscopic and morphometric study.
J Dermatol Surg Oncol 1989;15:149.
15. Bodian EL. Sclerotherapy. Semin
Dermatol 1987;6:238.
16. Sommer A, Van Mierlo PLH, Neumann
HAM, et al. Red and blue telangiectasia:
differences in oxygenation? Dermatol
Surg 1997;23:55.
17. Bean WB. Vascular spiders and related
lesions of the skin. Springfield, Ill.:
Charles C Thomas; 1958.
18. Apfelberg DB, Smith T, Maser MR,
et al. Study of three laser systems for
treatment of superficial varicosities of
the lower extremity. Lasers Surg Med
1987;7:219.
19. Apfelberg DB, Maser MR, Lash H,
et al. Use of the argon and carbon
dioxide lasers for treatment of
superficial venous varicosities of the
lower extremity. Lasers Surg Med
1984;4:221.
20. Frazzetta M, Palumbo FP, Bellisi M,
et al. Considerations regarding the use
of the CO
Laser 1989;2:4.
21. Landthaler M, Haina D, Waidelich W,
Braun-Falco O. Laser therapy of
venous lakes (Bean-Walsh) and
telangiectasias. Plast Reconstr Surg
1984;73:78.
22. Glaich AS, Goldberg LH, Dai T, et al.
Fractional photothermolysis for the
treatment of telangiectatic matting: A
case report. J Cosmet Laser Ther
2007;9:101.
23. Apfelburg DB, Maser MR, Lash H.
Argon laser management of cutaneous
vascular deformities. West J Med
1976;124:99.
24. Dixon JA, Rotering RH, Huethner SE.
Patient’s evaluation of argon laser
therapy of port-wine stain, decorative
tattoos, and essential telangiectasia.
Lasers Surg Med 1984;4:181.
25. Corcos L, Longo L. Classification and
treatment of telangiectases of the
lower limbs. Laser 1988;1:22.
26. Chess C, Chess Q. Cool laser optics
treatment of large telangiectasia of the
lower extremities. J Dermatol Surg
Oncol 1993;19:74.
27. Tan OT, Kerschmann R, Parrish JA.
Effect of skin temperature on selective
vascular injury caused by pulsed laser
irradiation. J Invest Dermatol
1985;85:441.
28. Bruck LB. Micro-contact argon laser
probe may enhance therapy,
laser: personal case study.
2
365
Chapter
https://t.me/med1917
13
Treatment of Leg Telangiectasias with Laser and High-Intensity Pulsed Light
366
Dermatology Times, p. 15, October,
1988.
29. Weiss RA, Weiss MA. Combination
intense pulsed light and sclerotherapy:
a synergistic effect. Presented at the
11th Annual Meeting of the North
American Society of Phlebology, Palm
Desert, Calif., November, 1997.
30. West TB, Alster TS. Comparison of the
long-pulse dye (590–595 nm) and
KTP (532 nm) lasers in the treatment
of facial and leg telangiectasias.
Dermatol Surg 1998;24:221.
31. Quintana AT, Grossman MG, Kauvar
ANB, et al. Removal of leg veins with
laserscope potassium titanyl
phosphate-532 nm and Dermaststat
2 mm handpiece. Presented at the
18th Annual Meeting of the American
Society of Laser Medicine and Surgery,
San Diego, Calif., April 5–7, 1998.
32. Adrian RM. Treatment of leg
telangiectasias using a long-pulse
frequency-doubled neodymium:YAG
laser at 532 nm. Dermatol Surg
1998;24:19.
33. McMeekin TO. Treatment of spider
veins of the leg using a long-pulsed
Nd:YAG laser (VersaPulse) at 532 nm.
J Cutan Laser Ther 1999;1:179.
34. Bernstein EF, Kornbluth S, Brown DB,
Black J. Treatment of spider veins
using a 10 millisecond pulse-duration
frequency-doubled neodymium YAG
laser. Dermatol Surg 1999;25:316.
35. Narurkar VA. The efficacy of the
Coherent VersaPulse 532 nm variable
pulse laser for the treatment of
superficial leg telangiectasia. Presented
at the 18th Annual Meeting of the
American Society of Laser Medicine
and Surgery, San Diego, Calif., April
5–7, 1998.
36. Massey RA, Katz BE. Successful
treatment of spider leg veins with a
high-energy, long-pulse, frequencydoubled neodymium:YAG laser
(Help-G). Dermatol Surg 1999;25:677.
37. Krause L. Regarding successful
treatment of spider leg veins.
Dermatol Surg 2000;26:169.
38. Fournier N, Brisot D, Mordon S.
Treatment of telangiectases with a
532 nm KTP laser in multipulse
mode. Dermatol Surg 2002;28:564.
39. Woo WK, Jasim ZF, Handley JM.
532-nm Nd:YAG and 595-nm pulsed
dye laser treatment of leg
telangiectasia using ultralong pulse
duration. Dermatol Surg 2003;29:
1176.
40. Raskin B, Fany RR. Laser treatment for
neovascular formation. Lasers Surg
Med 2004;34:189.
41. Sadick NS, Weiss R. The utilization of
a new yellow light laser (578 nm) for
the treatment of class I red
telangiectasia of the lower extremities.
Dermatol Surg 2002;28:21.
42. Goldman MP, Fitzpatrick RE.
Cutaneous laser surgery: the art and
science of selective photothermolysis,
2nd ed. St Louis: Mosby; 1998.
43. Garden JM, Tan OT, Kerschmann R,
et al. Effect of dye laser pulse duration
on selective cutaneous vascular injury.
J Invest Dermatol 1986;87:653.
44. Polla LL, Tan OT, Garden JM, Parrish
JA. Tunable pulsed dye laser for the
treatment of benign cutaneous
vascular ectasia. Dermatologica
1987;174:11.
45. Ashton N. Corneal vascularization. In:
Duke-Elder S, Perkins ES, editors. The
transparency of the cornea. Oxford:
Blackwell; 1960.
46. Folkman J, Klagsbrun M. Angiogenic
factors. Science 1987;235:442.
47. Ryan TJ. Factors influencing the
growth of vascular endothelium in the
skin. Br J Dermatol 1970;82(Suppl 5):
99.
48. Dvorak HF. Tumors: wounds that do
not heal: similarities between tumor
stroma generation and wound
healing. N Engl J Med 1986;315:
1650.
49. Majewski S, Kaminski M, Jablonska S,
et al. Angiogenic capability of
peripheral blood mononuclear cells in
psoriasis. Arch Dermatol 1985;121:
1018.
50. Nakagawa H, Tan OT, Parrish JA.
Ultrastructural changes in human skin
after exposure to a pulsed laser. J
Invest Dermatol 1985;84:396.
51. Tan TT, Carney JM, Margolis R, et al.
Histologic responses of port-wine
stains treated by argon, carbon
dioxide, and tunable dye lasers: a
preliminary report. Arch Dermatol
1986;122:1016.
52. Goldman MP, Martin DE, Fitzpatrick
RE, Ruiz-Esparza J. Pulsed dye laser
treatment of telangiectases with and
without subtherapeutic sclerotherapy:
clinical and histologic examination in
the rabbit ear vein model. J Am Acad
Dermatol 1990;23:23.
53. Goldman MP, Fitzpatrick RE.
Pulsed-dye laser treatment of leg
telangiectasia: with and without
simultaneous sclerotherapy. J
Dermatol Surg Oncol 1990;16:338.
54. Perez B, Nunez M, Boixeda P, et al.
Progressive ascending telangiectasia
treated with the 585 nm flashlamppumped pulsed dye laser. Lasers Surg
Med 1997;21:413.
55. Fajardo LF, Prionas SD, Kowalski J,
Kwan HH. Hyperthermia inhibits
angiogenesis, Radiat Res 1988;
114:297.
56. Sadick NS, Sorhaindo L. An evaluation
of post-sclerotherapy laser
compression and its efficacy in the
treatment of leg telangiectasias.
Phlebol 2006;21:191.
57. Reichert D. Evaluation of the
long-pulse dye laser for the treatment
of leg telangiectasias. Dermatol Surg
1998;24:737.
58. Hsia J, Lowery JA, Zelickson B.
Treatment of leg telangiectasia using a
long-pulse dye laser at 595 nm. Lasers
Surg Med 1997;20:1.
59. Bernstein EF. Then new-generation,
high-energy, 595 nm, long pulseduration, pulsed-dye laser effectively
removes spider veins of the lower
extremity. Lasers Surg Med 2007;39:
218.
60. Lee PK, Lask GP. Treatment of leg
veins by long pulse dye laser
(Sclerolaser). Lasers Surg Med
1997;9(Suppl):40.
61. Bernstein EF, Lee J, Lowery J, et al.
Treatment of spider veins with the
595 nm pulsed-dye laser. J Am Acad
Dermatol 1999;39:746.
62. Hohenleutner U, Walther T, Wenig M,
et al. Leg telangiectasia treatment with
a 1.5 ms pulsed dye laser and ice cube
cooling of the skin: 595 vs. 600 nm.
Lasers Surg Med 1998;23:72.
63. Alora MB, Stern RS, Arndt KA, Dover
JS. Comparison of the 595 nm long
pulse (1.5 ms) and ultra-long pulse
(4 ms) lasers in the treatment of leg
veins. Dermatol Surg 1999;25:445.
64. Polla LL. Treatment of leg
telangiectasia with a 595 nm LPDL.
Lasers Surg Med Suppl 2002;14:78.
65. Weiss RA, Weiss MA. Long pulsed dye
laser (LPDL) treatment of resistant
telangiectatic matting of the legs.
Lasers Surg Med Suppl 2002;14:86.
66. Woo WK, Jasim ZF, Handley JM.
532-nm Nd:YAG and 595-nm
pulsed dye laser treatment of leg
telangiectasia using ultralong pulse
duration. Dermatol Surg 2003;29:
1176.
67. Kono T, Yamaki T, Ercocen AR, et al.
Treatment of leg veins with the long
pulse dye laser using variable pulse
durations and energy fluences. Lasers
Surg Med 2004;35:62.
68. Adrian RM. Long pulse normal mode
alexandrite laser treatment of leg
veins. Presented at the 18th Annual
Meeting of the American Society of
Laser Medicine and Surgery, San
Diego, Calif., April 5–7, 1998.
69. McDaniel DH, Ash K, Lord J, et al.
Laser therapy of spider leg veins:
clinical evaluation of a new long
pulsed alexandrite laser. Dermatol
Surg 1999;25:52.
70. Izikson L, Nelson, JS, Anderson RR.
Treatment of hypertrophic and
resistant port wine stains with a
755-nm laser: A case series of 20
patients. Lasers Surg Med 2009;41:
427.
71. Kauvar ANB, Lou WW. Pulsed
alexandrite laser for the treatment of
leg telangiectasia and reticular veins.
Arch Dermatol 2000;136:1371.
72. Brunnberg S, Lorenz S, Landthaler M,
Hohenleutner U. Evaluation of the
long pulsed high fluence alexandrite
laser therapy of leg telangiectasia.
Lasers Surg Med 2002;31:359.
73. Ross EV, Meehan KJ, Gilbert S, et al.
Optimal pulse durations for the
treatment of leg telangiectasias with
an alexandrite laser. Lasers Surg Med
2009;41:104.
74. Eremia S, Li C, Umar SH. A side-by-
https://t.me/med1917
side comparative study of 1064 nm
Nd:YAG, 810 nm diode and 755 nm
alexandrite lasers for treatment of
0.3–3 mm leg veins. Dermatol Surg
2002;28:224.
75. Dierickx CC, Dugue V, Anderson RR.
Treatment of leg telangiectasia by a
pulsed 800 nm diode laser. Presented
at the 18th Annual Meeting of the
American Society of Laser Medicine
and Surgery, San Diego, Calif., April
5–7, 1998.
76. Trelles MA, Allones I, Álvarez J, et al.
The 800-nm diode laser in the
treatment of leg veins: assessment at 6
months. J Am Acad Dermatol
2006;54:282.
77. Garden JM, Bakus AD, Miller ID.
Diode laser treatment of leg veins.
Presented at the 18th Annual Meeting
of the American Society of Laser
Medicine and Surgery, San Diego,
Calif., April 5–7, 1998.
78. Wollina U, Konrad H, Schmidt W-D,
et al. Response of spider leg veins to
pulsed diode laser (810 nm): a
clinical, histological and remission
spectroscopy study. J Cosmet Laser
Ther 2003;5:154.
79. Kaudewitz P, Kloverkorn W, Rother W.
Effective treatment of leg vein
telangiectasia with a new 940 nm
diode laser. Dermatol Surg 2001;
27:101.
80. Kaudewitz P, Kloverkorn W,
Rother W. Treatment of leg vein
telangiectasias: 1-year results with a
new 940 nm diode laser. Dermatol
Surg 2002;28:1031.
81. Passeron T, Olivier V, Duteil L, et al.
The new 940-nanometer diode laser:
an effective treatment for leg
venulectasia. J Am Acad Dermatol
2003;48:768.
82. Chess C. Prospective study on
combination diode laser and
radiofrequency energies (ELOS™) for
the treatment of leg veins. J Cosmet
Laser Ther 2004;6:86.
83. Sadick NS, Trelles MA. A clinical and
histological, and computer-based
assessment of the polaris LV,
combination diode, and radiofrequency
system, for leg vein treatment. Lasers
Surg Med 2005;36:98.
84. Trelles MA, Martín-Vázquez, M, Trelles
OR, et al. Treatment effects of
combined radio-frequency current and
a 900 nm diode laser on leg blood
vessels. Lasers Surg Med 2006;38:185.
85. Prieto V, Zhang P, Sadick NS.
Comparison of a combination diode
laser and radiofrequency device
(Polaris®) and a long-pulsed 1064-nm
Nd:YAG laser (Lyra®) on leg
telangiectases. Histologic and
immunohistochemical analysis. J
Cosmet Laser Ther 2006;8:191.
86. Bone Salat C. Preliminary study on
varix treatment with laser. Presented
at the Pan-American Congress on
Phlebology and Lymphology,
Cordoba, Argentina, June 1–3, 2000.
87. Schroeter CA, Wilder D, Reineke T,
et al. Clinical significance of an
intense, pulsed light source on leg
telangiectasias of up to 1 mm
diameter. Eur J Dermatol 1997;7:38.
88. Goldman MP, Eckhouse S.
Photothermal sclerosis of leg veins.
Dermatol Surg 1996;22:323.
89. Hellwig S, Schroter C, Raulin C.
Behandlung essentieller
telangiektasien durch das Photoderm
VL. Z Hautk 1996;71:44.
90. Weiss RA, Weiss MA. Intense pulsed
light revisited: progressive increase in
pulse durations for better results on
leg veins. Presented at the 11th
Annual Meeting of the North
American Society of Phlebology, Palm
Desert, Calif., November 1997.
91. Schroeter CA, Neumann HAM.
An intense light source: the
PhotoDerm-VL flashlamp as a new
treatment possibility for vascular skin
lesions. Dermatol Surg 1998;24:743.
92. Green D. Pitfalls in the evaluation of
ablative therapy for telangiectases.
Dermatol Surg 1998;24:1143.
93. Green D. Photothermal removal of
telangiectasias of the lower extremities
with the PhotoDerm VL. J Am Acad
Dermatol 1998;38:61.
94. Raulin C, Weiss RA, Schonermark MP.
Treatment of essential telangiectasias
with an intense pulsed light source
(PhotoDerm VL). Dermatol Surg
1997;23:941.
95. Glassberg E, Lask GP, Tan EM, Uitto J.
The flashlamp-pumped 577-nm
pulsed tunable dye laser: clinical
efficacy and in vitro studies. J
Dermatol Surg Oncol 1988;14:1200.
96. Black JF, Wade N, Barton JK.
Mechanistic comparison of blood
undergoing laser photocoagulation at
532 and 1,064 nm. Lasers Surg Med
2005;36:155.
97. Cisneros JL, Del Rio R, Palou J.
Sclerosis and the Nd:YAG, Q-switched
laser with multiple frequency for
treatment of telangiectases, reticular
veins, and residual pigmentation.
Dermatol Surg 1998;24:1119.
98. Sadick NS, Weiss RA, Goldman MP.
Advances in laser surgery for leg veins:
bimodal wavelength approach to
lower extremity vessels, new cooling
techniques, and longer pulse
durations. Dermatol Surg 2002;
28:16.
99. Sadick NS. A dual wavelength
approach for laser/intense pulsed light
source treatment of lower extremity
veins. J Am Acad Dermatol
2002;46:66.
100. Weiss RA, Weiss MA. Initial results
with a new synchronized pulsed
1064 nm laser for larger telangiectasia.
Lasers Med Surg 1999;11(Suppl):21.
101. Weiss RA, Weiss MA. Early clinical
results with a multiple synchronized
pulse 1064 nm laser for leg
telangiectasias and reticular veins.
Dermatol Surg 1999;25:399.
102. Sadick NS. The utilization of a new
Nd:YAG pulsed laser (1064 nm) for
the treatment of varicose veins. Lasers
Med Surg 1999;11(Suppl):21.
103. Goldman MP. Treatment of leg
telangiectasia with three different
1064 nm lasers. Presented at the 24th
Annual Hawaii Dermatology Seminar,
The Big Island, Hawaii, Feb 7, 2000.
Published as: Laser treatment of leg
veins with 1064 nm long-pulsed
lasers. Cosmet Dermatol 13:27, 2000.
104. Weiss MA, Weiss RA. Three year results
with the long pulsed Nd:YAG 1064
laser for leg telangiectasia. Presented
at the Annual Meeting of the
American Society for Dermatologic
Surgery, Dallas, Tex., October 2001.
105. Sadick NS. Long-term results with a
multiple synchronized-pulse 1064 nm
Nd:YAG laser for the treatment of leg
venuelectasias and reticular veins.
Dermatol Surg 2001;27:365.
106. Trelles MA, Allones I, Martin-Vazquez
MJ, et al. Long pulse Nd:YAG laser for
treatment of leg veins in 40 patients
with assessments at 6 and 12 months.
Lasers Surg Med 2004;35:68.
107. Bowes LE, Goldman MP. Treatment of
leg telangiectasias with a 1064 nm
long pulse Nd:YAG laser using
dynamic vs contact cooling: a
comparative study. Laser Surg Med
Suppl 2002;14:40.
108. Eremia S, Li CY. Treatment of leg and
face veins with a cryogen spray
variable pulse width 1064-nm
Nd:YAG laser – a prospective study of
47 patients. J Cosmet Laser Ther
2001;3:147.
109. Li CY, Eremia S. Treatment of leg and
face veins with a cryogen spray,
variable pulse width 1064 nm
Nd:YAG laser – a prospective study of
47 patients. Am J Cosmet Surg
2002;19:3.
110. Lupton JR, Alster TS, Romero P.
Clinical comparison of sclerotherapy
versus long-pulsed Nd:YAG laser
treatment for lower extremity
telangiectases. Dermatol, Surg
2002;28:694.
111. Rogachefsky AS, Silapunt S, Goldberg
DJ. Nd:YAG laser (1064 nm)
irradiation for lower extremity
telangiectasias and small reticular
veins: efficacy as measured by vessel
color and size. Dermatol Surg
2002;28:220.
112. Omura NF, Dover JS, Arndt KA,
Kauvar ANB. Treatment of reticular leg
veins with a 1064 nm long-pulsed
Nd:YAG laser. J Am Acad Dermatol
2003;48:76.
113. Coles MC, Werner RS, Zelickson BD.
Comparative pilot study evaluating
the treatment of leg veins with a long
pulse Nd:YAG laser and sclerotherapy.
Lasers Surg Med 2002;30:154.
114. Sadick NS. Laser treatment with a
1064-nm laser for lower extremity
class I-III veins employing variable
spots and pulse width parameters.
Dermatol Surg 2003;29:916.
References
367
Chapter
https://t.me/med1917
13
115. Mordon S, Brisot D, Fournier N.
Using a ‘non uniform pulse sequence’
can improve selective coagulation
with a Nd:YAG laser (1.06 µm) thanks
to met-hemoglobin absorption: a
clinical study on blue veins. Lasers
Surg Med 2003;32:160.
116. Levy JL, Elbahr C, Jouve E, Mordon S.
Comparison and sequential study of
long pulsed Nd:YAG 1,064 nm laser
and sclerotherapy in leg telangiectasias
treatment. Lasers Surg Med
2004;34:273.
117. Galeckas KJ, Uebelhoer NS. Successful
treatment of pyogenic granuloma
using a 1,064-nm laser followed by
glycerin sclerotherapy. Dermatol Surg
2009;35:530.
118. Weiss RA, Weiss MA. Photothermal
sclerosis of resistant telangiectatic leg
and facial veins using the PhotoDerm
VL. Presented at the Annual Meeting
of the Mexican Academy of
Dermatology, Monterey, Mexico,
April 24, 1996.
119. Goldman MP. Are lasers or noncoherent light sources the treatment
of choice for leg veins? A look into
the future. Cosmet Dermatol 2001;
14:58.
Treatment of Leg Telangiectasias with Laser and High-Intensity Pulsed Light
368
C H A P T E R
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Venoactive Drugs
Albert-Adrien Ramelet
14
Introduction
Venoactive drugs (VAD) are a heterogeneous group of medicinal products, of plant or synthetic origin, which have effects
on edema (C3) and on symptoms related to chronic venous
disease (CVD, classes C0s–C6s according to the CEAP classification).
VAD are active on venous pain, which does not respond to
anti-inflammatory drugs.
varicose vein prevention. Flavonoids may be an adjuvant
factor to leg ulcer healing.
protective agents, phlebotonics, venotonics, vasoprotectors,
phlebotropics, and venotropics. These names should be discarded, as a standardization of appellations is highly desirable.
1,2
A specific ‘pain-killer’ effect has been suggested, as
1–5
VAD have no demonstrated effect on varicose veins or in
Many names have been used to describe VAD: edema-
The main mechanisms of action of VAD are:
• increasing venous tone (this results in restoration of
normal blood flow, dispersion of red cell aggregates, and
better oxygenation)
• improving capillary hyperpermeability and lymph flow
(thus protecting the microcirculation and decreasing the
risk of edema)
• inhibiting the leukocyte adhesion to endothelial cells
and the transmigration of leukocytes into the venous
wall (presently demonstrated only for micronized
purified flavonoid fraction (MPFF))
• improving fibrinolysis and blood rheology.
As a consequence of lack of interest in CVD, publications
devoted to VAD are scattered in journals of different languages, which are not always indexed in PubMed.
Although most authors are certainly perfectly honest, it
must be emphasized that one group has been accused of
fraudulent behavior. As their studies have already been published, they are, unfortunately, still available in reviews and
meta-analyses.
Effectiveness of VAD has been regularly discussed, mostly
by pharmacologists. Some of them have a poor knowledge of
phlebology and VAD; their assertions are debatable. Others
are not aware of the difficulty of assessing the activity of
13
VAD.
Symptoms are subjective, although they can be correctly quantified. Clinical signs such as edema are not easy to
measure, owing to significant daily variations in each individual. Efficacy of VAD on edema and venous symptoms may
currently be considered as correctly established. However, there
is a need for further randomized, controlled clinical trials with
greater attention paid to methodological quality.
1–14
13–15
Classification of VAD
The various classes of VAD are shown in Table 14.1.
1–3
In this chapter, we shall distinguish VDA as:
• benzopyrones
• saponins
• other plant extracts
• synthetic drugs.
Benzopyrones
This large group of medicines contains many substances,
which are often closely related and endowed with multiple
pharmacologic properties. Benzopyrones (alpha-pyrones and
gamma-pyrones) are obtained from many indigenous and
exotic plants, often used in traditional medicine. They belong
to the family of phytophenols, and are related to resveratrol,
which is currently undergoing a wide range of studies to
assess its possible preventative and therapeutic value in
atherosclerosis.
Alpha-benzopyrones
Coumarin (1,2-benzopyrone; 5,6-benzo-alpha-pyrone) has
been used either alone (mainly for the treatment of lymphedema) or in low doses in combination with oxerutin.
Esculetin (6,7-dihydroxycoumarin) and umbelliferone
(7-hydroxycoumarin) are coumarin derivatives. Dicoumarols
(dimers of 4-hydroxycoumarins) are powerful oral anticoagulants (acenocoumarol, phenprocoumon, warfarin). Their
therapeutic properties thus differ fundamentally from those
of VAD, despite their chemical similarities.
Coumarin is quickly absorbed and has a short half-life
of 1 hour. Both it and its metabolites are excreted via the
kidney.
Coumarin induces proteolysis of high-molecular-weight
proteins present in lymphedema. Small-size protein fragments
can then be more easily drained via the lymphatics. The
oncotic pressure drops and edema lessens. However, effectiveness is debatable.
have an antiedematous effect, they do not modify the coagulation of blood, in contrast to dicoumarols. Alongside its therapeutic properties, the aromatic properties of coumarin are
extensively used in spices for cooking, cosmetology (soap,
perfumes) and the tobacco industry.
Several cases of drug-related hepatitis have been reported
after taking high doses of coumarin or dicoumarols as an
anticoagulant. Coumarin has been withdrawn from the market
for this reason, except in brands associating low doses of
coumarin and troxerutin.
Gamma-benzopyrones (flavonoids)
These have been previously defined as ‘vitamin P’ or factor P
(permeability), as flavonoid deficiency results in capillary fragility and increased vessel wall permeability in the animal.
These appellations are obsolete.
16
17
Although coumarin and its derivatives
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14
Venoactive Drugs
Table 14.1 Classification of the main venoactive drugs
Group Substance Origin Dosage (mg/day) Pregnancy Breastfeeding
BENZOPYRONES
Alpha-benzopyrones Coumarin Melilot (Melilotus
Gammabenzopyrones
(flavonoids)
SAPONINS
OTHER PLANT EXTRACTS
SYNTHETIC PRODUCTS
+: the product has been administered during pregnancy.
?: the manufacturer gives no indication, making the physician responsible for the decision!
Diosmin Citrus spp.
Micronized purified
flavonoid fraction
Rutin and rutosides
O-(β-hydroxyethyl)-
rutosides (troxerutin,
HR)
Escin Horse chestnut
Ruscus extract Butcher’s broom
Anthocyans Bilberry (Vaccinium
Proanthocyanidines
(oligomers)
Ginkgo biloba Ginkgo biloba L. 2 ampules or
Calcium dobesilate Synthesis 1000 to 1500 – – 2 to 3
Benzarone Synthesis 400 to 600
Naftazone Synthesis 30
officinalis L.)
Woodruff (Asperula
odorata L.)
Sophora japonica L.
Rutaceae aurantiae 1000
Sophora japonica L.
Eucalyptus spp
Fagopyrum
esculentum Moench
seed (Aesculus
hippocastanum L.)
(Ruscus aculeatus L.)
myrtillus L.)
Grape pips (Vitis
vinifera)
Maritime pine
(Pinus maritima
Lank) (Pycnogenol)
90 combined with
troxerutin (540)
300–600
1000
120, then 60 ? – 3
2 to 3 tablets
116 ? – 2
100 to 300
300 to 360 ? – 3
capsules (extracts of
Ginkgo, heptaminol
and troxerutin)
+
+
+
+
+
+
– – 2
+
+
– 3
– 1 or 2
– 1 or 2
– 1 or 2
– 2 to 3
– 1 to 3
– 2 to 3
– 1
Number of
Intakes Per Day
Many plant pigments belong to this group. They are used
in the form of plant extracts, in semisynthetic or synthetic
preparations. The main distinction is between:
• flavone and its derivatives, flavonols (kaempferol,
diosmetin, diosmin, hidrosmin, quercetin, rutin
(rutoside, oxerutin))
• flavanes (or flavonones): hesperitin, hesperidin and its
derivatives, Pycnogenol, procyanidolic oligomers, etc.
Substances mostly used therapeutically in CVD are
described below.
Diosmin and Micronized Purified Flavonoid Fraction
Diosmin (3′,5,7-trihydroxy-4′-methoxyflavone-7-rhamnoglucoside) is extracted from plants (rutaceae) or obtained by
synthesis (as another bioflavonoid, hidrosmin).
of diosmin is 8 to 12 hours, with its elimination being renal
(65%) and biliary (35%).
370
19
The half-life
Micronization enables a decrease in particle size of the
flavone fraction from 20 to 2 µM (MPFF
ing the intestinal absorption and bioavailability of the substance, as has been demonstrated in two clinical trials.
20–45
), thereby increas-
22–27
Diosmin and MPFF act:
• On venous tone, indirectly, by inhibiting the breakdown
of norepinephrine (noradrenaline) by COMT (catecholO-methyltransferase). Noradrenergic activity is thereby
prolonged and venous tone increased. The degree of this
effect varies in linear relation to the dose administered.
• On lymphatic drainage: decrease in the diameter of
lymphatic vessels and intralymphatic pressure, increased
number of functional lymphatics, and lymphatic flow
and peristalsis, as well as capillary hematocrit and red
cell velocity.
• On the microcirculation: protection of microvascular
permeability via inhibition of adhesion of leukocytes,
their intratissue migration, the release of inflammatory
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mediators and the expression of certain leukocyte
(L-selectin) and endothelial (ICAM-1, VCAM-1) adhesion
substances initiating the inflammatory events leading to
raised microcirculatory venous pressure.
MPFF is indicated in the treatment of edema and of
symptoms related to venous insufficiency (edema, heavy legs,
discomfort, pruritus, night cramps, pain, swelling), pelvic
congestion syndrome,
erative pain and more rapid recovery
42
venous surgery (decrease in postop-
43,44
) as well as lymphedema, including filarial.45 Its other indications are
gynecological (tense painful breasts, IUD-related bleeding)
and proctological.
All of these effects have been confirmed in double-blind
clinical trials,
20–44
which also showed a significant improvement in the quality of life of patients suffering from (chronic
venous insufficiency) CVI. According to five clinical trials
joined in a meta-analysis, MPFF may hasten the healing of leg
41
ulcers.
Rutosides and Oxerutin
A standard mixture of several flavonoid derivatives is obtained
by hydroxyethylation of a natural substance, rutin. Troxerutin
is a fraction of oxerutine. Absorbed by the digestive tract,
oxerutine has a half-life of 24 hours and is principally excreted
in bile. A large number of pharmacological and clinical
46–58
studies
have provided evidence of its influence on disturbances of capillary permeability, effects on erythrocyte deformation and aggregation, antiedematous actions, and inhibition
of prostaglandin synthesis. Its diffusion and accumulation in
the venous wall have been demonstrated.
54
Rutosides are indicated as an antiedematous agent in
venous disorders, in proctology (hemorrhoids) and in ophthalmology (retinopathy). Following topical application,
oxerutine is absorbed and its action on cutaneous capillary
fragility has been demonstrated.
Saponins
Escin
Escin is a mixture extracted from horse-chestnut seed
(HCSE) containing many compounds, such as protoescigenin, barringtogenol, alpha- and beta-escin, cryptoescin, and
benzopyrones.
HCSE compounds are poorly absorbed in the digestive tract
(12.5%). Maximum activity of the preparation occurs 16
hours after ingestion. Escin and its metabolites are eliminated
via the kidney and gallbladder; its percutaneous absorption
has also been demonstrated.
Escin increases venous wall tone and has a welldemonstrated antiedematous effect.
have been evaluated in one Cochrane study, curiously excluding other VADs.
12
Ruscus
Extracts of ruscus (butcher’s broom) contain saponins and
flavonoids. The precise composition of these extracts is
poorly understood. Venotonic and antiedematous actions
have been well demonstrated in open and randomized
controlled trial (RCT) studies and are associated with
a reduction of symptoms in patients suffering from
65–74
CVD.
59–64
The HSCE extracts
Extracts of Centella asiatica
79,80
are believed to enhance colla-
gen synthesis in connective tissue.
Many other plants are used in the treatment of symptoms
of CVD. All of them contain flavonoids among other active
substances: procyanidolic oligomers (anthocyans in bilberry
extracts; proanthocyanidols in white grape pit, Vitis vinifera,
maritime pine (Pycnogenol)
83–85
).
81,82
Phytotherapy
Plant extracts used in phytotherapy are often poorly standardized and controlled. Their active substance content may vary
according to plant genetics, as well as to climatic factors,
quality of the ground in which the plants were grown, the time
of harvesting, and the extraction methods. Flavonoids may be
at least partially responsible for their pharmacologic effects,
but other glycosides might also be active.
Nutritional supplement
Nutritional supplements are a new trend. Some brands have
been introduced in countries where VAD are not available, or
as a new commercial over-the-counter (OTC) channel. They
contain vegetal derivatives, mostly polyphenols, and antioxidants in order to relieve the symptoms of CVD.
Other preparations used in the past
Dihydroergotamine and dihydroergocristine (rye ergot extract)1
are no longer used in CVD treatment.
Synthetic drugs
Calcium dobesilate
This synthetic substance (dihydroxy-2,5-benzene-calcium sulfonate) is well absorbed after oral administration. Plasma
levels are maximal 6 hours after ingestion. The half-life is short
(5 hours).
The drug is eliminated principally in the urine, without
being metabolized. It is absorbed following topical application.
Calcium dobesilate decreases capillary permeability and
blood viscosity, and improves lymphatic drainage.
antiedematous effect persists for about 2 months after treatment is stopped.
Benzarone
Benzarone, or (2-ethyl-1-benzofuran-3-yl)-(4-hydroxyphenyl)
methanone is well absorbed following oral administration. Its
half-life is about 10 hours. It is eliminated with its metabolites
by the kidney. Benzarone has fibrinolytic properties and
inhibits platelet aggregation.
Several cases of severe hepatitis have been reported.
tosensitization may occur during treatment.
Naftazone
Beta-naphtoquinone monosemicarbazone or naftazone
is rapidly absorbed from the digestive tract. Its half-life
is short (1.5 hours) and its metabolites are eliminated
in urine.
A venoconstrictor effect and lowering of serum betaglucuronidase levels have been demonstrated following the
administration of 30 mg a day of naftazone. This substance
might act on vessel wall permeability and on abnormalities of
endothelial cells seen in CVD.
86–96
97
The
Pho-
98,99
Classification of VAD
Other plant extracts
Extracts of Ginkgo biloba
Antagonists of platelet activating factor (PAF), they have an
action on platelet aggregation, blood viscosity, and edema.
75–78
contain terpens and flavonoids.
Tribenoside
Ethyl-3,5,6-tri-O-benzyl-D-glucofuranoside or tribenoside is a
glucose derivative.
istration and is believed to have a half-life of about 24 hours.
1
It is well absorbed following oral admin-
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14
Venoactive Drugs
Its metabolites are excreted in the urine. Tribenoside can also
be used by topical application.
Tribenoside decreases capillary permeability and has antiinflammatory and analgesic actions. The usefulness of this
preparation is limited by the frequency of its adverse effects:
digestive and, above all, cutaneous (up to 7.2%). Presently it
has been abandoned.
Principal Mode of Action of VAD
VAD have a demonstrated positive action on:
• edema: decrease in capillary permeability, improved
lymphatic drainage
• venous tone
• microcirculation: inhibition of leukocyte adhesion and
migration, inhibition of inflammatory mediator release
and prostaglandin synthesis, antioxidant effects (anti-free
radicals), decrease in blood viscosity
• erythrocytes: inhibition of aggregation, decrease in
erythrocytic deformation.
Administration, Dosage, Limits
in the event of re-emergence of the symptoms after treatment
discontinuation.
2
Premenstrual syndrome
A particular dosage regimen (intake restricted to the last 2
weeks of the menstrual cycle) has been recommended for
women presenting with premenstrual syndrome with pain
and edema of the legs.
100–102
Pregnancy and lactation
Some VAD have been used without any problems during the
second and third trimester of pregnancy to relieve edema and
symptoms of CVD and have been effective.
103–105
They are indicated in Table 14.1. The pharmaceutical companies do not
advise administration during pregnancy, however, and generally recommend that VAD should not be administered during
breastfeeding.
Topical application
Topical VAD preparations are also available (rutosides,
diosmin, escin, calcium dobesilate, among others). Absorption of the active drug has been demonstrated to have a degree
of efficacy in a few double-blind studies.
106,107
VAD are mainly administered orally. The drug substances of
plant origin are frequently poorly absorbed. Absorption may
be enhanced by various chemical devices, hydroxyethylation
of rutosides or micronization (MPFF).
Usual dosages are mentioned in Table 14.1. Low VAD
doses should not be prescribed, as they are ineffective.
binations of different preparations, whose value has not been
validated by clinical trials, is to be avoided.
2
1,2
Com-
Adverse effects
Safety is in general good. Adverse effects occur in about 5%
of the patients treated (Table 14.2). The side effects are rarely
severe and comprise:
• dizziness, headache
• minor gastrointestinal disorders: ‘heavy’ stomach,
flatulence, rarely nausea and vomiting, constipation and
diarrhea
• rare skin rashes.
Duration of treatment
A course of VAD treatment generally lasts 1 month. It is not
appropriate to prescribe a VAD for more than 3 months except
Table 14.2 Adverse effects of venoactive drugs
Substance Skin Rashes* Gastrointestinal Disorders
Coumarin and rutosides
Oxerutin and rutosides
Escin (horse chestnut)
Ruscus extracts
Anthocyans
Proanthocyanidines and pycnogenol
Ginkgo biloba
Diosmin and micronized purified flavonoid fraction
Calcium dobesilate
Benzarone
Naftazone
*Skin rashes: undefined.
†
Gastrointestinal disorders (minor): inappetence, nausea, constipation, diarrhea.
‡
Hepatitis: after intake of coumarin (high doses) and benzarone.
§
Agranulocytosis: some cases reported; however, most of them in the same town. Less than expected ratio of agranulocytosis in the general population.
+ +
+ +
+ +
+ +
+ +
+ +
+
However, the intake of benzarone or of high doses of coumarin (400 mg/day) has been associated with hepatitis. Prescription of these drugs is debatable. Coumarin has been
†
Other Adverse Effects
Hepatitis‡ (high-dose coumarin only)
+
+
+
+
Urticaria
Fever agranulocytosis
Photosensitization hepatitis
Headache dizziness
3
372
withdrawn from most occidental countries. Low doses of cou-
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marin combined with rutosides, marketed in certain countries, do not appear to induce such complications.
Several cases of agranulocytosis were associated with
calcium dobesilate (but with a possible causal relationship in
only some cases). Nine of these cases were reported in Spain
since the product was first marketed over 35 years ago. Currently to the best of our knowledge, the incidence of agranulocytosis with calcium dobesilate treatment is less than the
spontaneous prevalence in the overall population.
Scientifically Recognized Indications
Main indications of VAD
These are:
• edema
• subjective symptoms related to varicose veins or
attributed to CVD (heavy legs, ‘heaviness’, ‘discomfort’,
pruritus, pain along varicose vein paths)
• minor specific but frequently associated symptoms
(paresthesia, night-time cramps, or restless leg
syndrome).
score of the assessments range from 54% to 76% for the
drug substance and 18% to 46% for the placebo groups.
• the articles were frequently published in phlebological
journals that are not indexed.
• university departments have little interest in CVD and
scarcely contribute to the international studies.
• some pharmacologists reject VAD without being
sufficiently aware of the dossiers on those drugs.
Demonstrated therapeutic effect
More than 130 RCTs or meta-analyses have been published to
validate the clinical effectiveness of VAD.
tions have been evaluated in Cochrane reviews,
reviews,
Siena.
15
and in consensus meetings, as in Paphos4 and
3
Recommendations according to three levels of evidence –
A, B, and C – may be suggested after a critical review of the
different papers devoted to VAD (Table 14.3):
• Grade A: RCT with large sample sizes, valid
meta-analyses
• Grade B: RCT with small sample size
• Grade C: Other controlled trials, no RCTs.
17–107
These publica-
13,64
in other
Conclusions
Leg ulcer
Double-blind studies using MPFF
have demonstrated an adjuvant effect on healing of leg ulcers
when larger than 5 cm2 and existing for more than 6 months.
Pain was relieved in all treated patients.
Long-term administration of rutosides did not prevent leg
ulcer relapses in one study.
29,40
and one meta-analysis41
46
Other indications
These include:
• prophylaxis of edema following long flights
• premenstrual syndrome
• pelvic congestion syndrome
• prevention of pain after venous surgery.
42
43,44
However, the indications vary depending on the country.
Venoactive drugs may also have been registered for other
indications such as episodes of hemorrhoids or diabetic
retinopathy.
Combination with compression
Elastic compression is considered as the first-line treatment of
CVD; VAD may:
• accentuate the effect of compression
47,52,55
• be prescribed instead of compression when compression
is contraindicated (arterial insufficiency, sensitive
neuropathies) or poorly tolerated (individual reactions,
summer heat).
3,60
Results
The evaluation of VAD is complex since:
• the objective assessment of edema and of the
attenuation of symptoms is difficult and subject to
criticism.
• the placebo effect is marked even though the drug
substance effect is statistically greater. Thus, the overall
Guidelines
Scientific societies have published guidelines with the purpose
of developing double-blind trials whose parameters are
incontestable.
14
The American Venous Forum in its Guidelines suggests
the use of VAD (as MPFF and rutosides) in hot climates when
the wearing of stockings is less acceptable. MPFF might be a
useful adjunct to conventional therapy in large and longstanding ulcers which might otherwise be expected to heal
108
slowly.
In patients with persistent venous ulcers, the American
College of Chest Physicians suggest that MPFF administered
orally be added to local care and compression.
109
Conclusions
Although not available in the United States, VAD are widely
used in the world in the interest of patients.
They have no demonstrable effect on varicose veins or in
varicose vein prevention, but they are effective on edema (C3)
and on symptoms related to CVD (C0s–C6s), or as an adjuvant factor to leg ulcer healing. A specific ‘pain-killer’ effect
has been suggested, as VAD are active on venous pain, which
does not respond to anti-inflammatory drugs.
Successful treatment of venous symptoms is cost-effective.
Renouncement of the use of VAD may induce an augmentation of health budget in the mid term, as demonstrated by
Allegra.
CVD, the complications from venous disorders will surmount,
inducing higher expenses: nonsteroidal anti-inflammatory
drugs may be prescribed for venous pain, with expensive side
effects; days off work may increase, among other effects of
insufficient and late treatment of CVD, including alteration to
quality of life.
sold, it is no more acceptable for drug substances that have
long been in use, and whose efficacy has been demonstrated,
to be sacrificed for political reasons.
paid to methodological quality, in order to establish more
accurately the place of VAD in the treatment of CVD.
110
If patients do not present early for symptoms of
While it is not acceptable for ineffective medications to be
Further clinical RCTs are desirable, with greater attention
373
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