Monday, April 18, 2011

Topical Treatment of Hypertensive Leg Ulcers – an Article Review

Updated 3/2017-- all links (except to my own posts) removed as many no longer active. 

An interesting little article in the April issue of the Archives of Dermatology (full reference below) by Senet and colleagues on the treatment of hypertensive leg ulcers with platelet-derived growth factor-BB.  Interesting, in that, it reported a negative outcome or lack of superiority for one treatment over another.
First, what is a hypertensive leg ulcer (HLR)?
According to the Graves and colleagues (second article referenced below), Martorell, a Spanish cardiologist (1906-1984) first noticed the relationship between hypertension and alterations in arterioles and leg ulcers in 1945.  Martorell called these ulcers hypertonic or hypertensive ulcers of the legs and published the first 4 cases. 
Originally, Martorell described the following diagnostic criteria:
a) Ulcer located anterolaterally on the lower legs,
b) arterial diastolic hypertension of the lower legs,
c) hyperpulsatility of the arteries of the lower legs,
d) absence of arterial calcification,
e) absence of CVI (chronic venous insufficiency),
f) symmetric lesions (either ulceration at the same time or as a result of previous ulceration of the opposite leg),
g) increased pain in horizontal position, and
h) female sex.
Graves also noted that soon after Martorell reported his 4 cases, 11 other cases were published by Hines and Farber confirming the existence of these ulcers -- thus, the ulcer is also called the "hypertensive ulcer of Hines-Farber."
Senet and colleagues note, “Hypertensive leg ulcers (HLUs), first described in the 1940s, were renamed Martorell HLUs or necrotic angiodermatitis by American and European dermatologists.”
So HLU’s are also known as “hypertensive ulcer of Hines-Farber” and as necrotic angiodermatititis.
Whatever it is called, HLR’s are extremely painful, superficial, rapidly spreading, necrotic wounds on the dorsolateral part of the leg which have red purpuric margins.  The pathophysiologic characteristics of HLUs include dermal and subdermal vessel arteriosclerosis, inappropriate local vasoconstriction, but no significant involvement of the large deeper vessels.
Senet and colleagues note the medical management of HLU is currently symptomatic: controlling hypertension and diabetes, wound debridement, and application of the usual dressings.  Surgical management is often skin grafts.
Senet and colleagues conduced a multicenter, randomized controlled trial from March 2004 to June 2009 to determine the effect of topical becaplermin gel on HLU healing.
Eligible participants (n=59) were randomly assigned to receive either topical becaplermin gel-BB, 0.01% (Regranex gel) or hydrogel (Duoderm Hydrogel).
For both groups, treatment began 1 week after randomization, during the second visit (week 0), and all patients received the same daily local care: wound irrigation with normal saline, application of a continuous thin layer of gel on the wound, covering with a moist saline gauze and a bandage.
Each reference wound surface was estimated on treatment day 1 by measuring wound length and width to determine the appropriate becaplermin gel or hydrogel volume to apply that was maintained throughout the study [a single 15-g tube is enough to treat a 5-cm2 wound for 6 weeks (1 cm of gel/cm2/d)].
The patient or his/her caregiver was instructed on proper wound care, gel application, and wound dressing, which was continued until complete healing or for a maximum of 8 weeks.   All patients were observed through week 12.
Topical becaplermin, compared with hydrogel dressing, did not improve the complete wound closure rate (primary outcome measure) after treatment week 8 and had no significant effect on quality of life, pain, or median wound area.
Complete wound closure rates for becaplermin and hydrogel, respectively, were 18% (5 of 28 patients) and 10% (3 of 31 patients), respectively, at week 8 (an 8 percentage-point difference; 95% confidence interval [CI], –10.3 to 26.0) and 36% (10 of 28 patients) and 26% (8 of 31 patients) at week 12 (10 percentage-point difference; 95% CI, –13.6 to 33.4).

1.  Topical Treatment of Hypertensive Leg Ulcers With Platelet-Derived Growth Factor-BB: A Randomized Controlled Trial; Patricia Senet; Eric Vicaut; Nathalie Beneton; Clelia Debure; Catherine Lok; Olivier Chosidow; Arch Dermatol. 2011;0(2011):archdermatol.2011.84. 
2.  Martorell Hypertensive Leg Ulcer:  Case Report and Concise Review of the Literature; Graves JW, Morris JC, Sheps SG. J Human Hypertension. 2001;15:279-283. (pdf file)
3.  Las ulcers supramalleolares por arteriolitis de las grandes hipertensas; Martorell F.;  Actas del Instituto Policlinico de Barcelona. 1945;1:6-9. (not read by me)
4.  Ulcer of the leg due to arteriosclerosis and ischemia occurring in the presence of hypertensive disease; Hines EA Jr, Farber EM.; Mayo Clin Proc. 1946;21:337-346.  (not read by me)

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