Dr. Hashim Al- Sayed (corresponding author)
Dr. Hashim Al- Sayed
Consultant, Family Medicine,
Director of Umm Gwalina H.C
P.O. Box .3050
Hamad Medical Corporation
email: fmcc2000@gmail.com

Mohamed H.,
AL-Maseeh F.,
Al-Lenjawi B.,
Al-Kozaaei D,
Al-Bader A.,
Abdeen J.

 

INTRODUCTION

Varicose ulceration has a significant prevalence and morbidity and places a considerable burden on health resources internationally (1,2). Chronic lower limb ulceration is common and may have a protracted course when, despite the best available treatments, some ulcers fail to heal.(3) Although there is no racial predilection, women seem more likely to develop venous ulcers than men (4) with a peak prevalence between 60 and 80 years of age (5,6) but 22% of people develop venous ulcers by 40 years of age leading to a substantial reduction in work productivity (7, 8). Consequently accurate diagnosis and optimal management are essential to promote speedy recovery and to prevent relapses.

The mechanisms by which venous hypertension, a prerequisite for venous ulcers, plays a role in the development of venous ulceration remains unclear although recent data suggest the involvement of pericapillary fibrin cuff deposition, fibrinolytic system dysregulation, entrapment of growth factors by macromolecules in the dermis and leukocyte plugging in the venous system of the lower limbs.(9-11).

Venous ulcers are painful with as many as three-quarters of patients reporting adverse effects on their quality of life (12,13). Several risk factors for venous ulceration have been proposed including leg injury (14), obesity, family history of varicose veins, phlebitis, occupations requiring standing for long periods, and previous surgery for varicose veins (15,16). They are characteristically located over the medial malleolus or gaiter area. The ulcer bed tends to be shallow with fibrinous material and granulation tissue. Venous disease of long duration causes indurations and fibrosis of the dermis and subcutaneous layer and when coupled with lower limb edema, an inverted bottle appearance results (16).

In February 2008, an otherwise healthy 38-year-old Egyptian male presented with a large varicose ulcer over the medial aspect of the right lower limb (Figure 1) that had persisted in spite of intensive therapy for the previous six years. He had no medical history apart from varicose veins in both lower limbs but there was a family history of venous insufficiency.

He was obese with a BMI of 32; phlebologic examination showed chronic venous insufficiency. There was a superficial painful ulcer measuring 4 x 7 cm on an edematous lower half of the leg, above and around the ankle, distal to the medial malleolus (gaiter area). The edges of the ulcer were irregular; the base was superficial with an exudate and slough. The surrounding skin was erythematous with increased warmth.

Palpation of peripheral pulses was difficult due to edema with normal sensation using 10 g monofilament. Initially the ulcer was cleaned with normal saline using a 20-gauge needle for irrigation; light debridement removed the slough and non-vital tissues and was followed by the application of Nu-gel, (Johnson & Johnson), a hydrogel consisting of a matrix of insoluble polymers with up to 90% water content enabling the donation of water molecules to the wound surface thereby transmitting vapour and oxygen. This is claimed to promote wound debridement by rehydration of non-viable tissue and to facilitate natural autolysis in the management of sloughing or necrotic wounds (55-58).
Silvercel hydro-alginate dressing is a controversial treatment for varicose ulcers that is discussed further below. In this case it was used and covered with 3-layer bandaging including one compression bandage applied in a 50% overlapping fashion to exert a gradual pressure greatest distal to the toes and reducing progressively to the anterior tibial tuberosity. Systemic treatment included oral micronized purified flavonoid fraction (Daflon: Servier) 500mg twice daily. The patient was instructed to rest in bed with the limb elevated for the first three days. Bandages and dressing with silver cell were changed every three days. Re-epithalization started at the wound edges and, later, islands of epithelium could be seen in the middle of the ulcer that represented keratinocyte out-growth from the hair follicles (44,45) producing complete resolution within one month. (Figures 2,3,4). The patient was also counseled regarding an average weight loss of 5 kg using the portion control (one dahoo-plate) method. He refused prophylactic compressive treatment, although some authors believe that compressive therapy constitutes the most important part of the conservative therapy of chronic venous insufficiency (43), but agreed to maintenance Daflon therapy. Follow up of the patient at three and six months showed intact skin (Figure 4).
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Recognised modifiable risk factors for varicose vein disease include occupations involving long periods of standing, and obesity (59,60) since it is thought that obesity leads to an increase in intra-abdominal pressure that impedes venous return from the lower extremities (61). Sugerman and colleagues demonstrated that weight loss is associated with correction of venous stasis in almost all patients (62).

Suggested modalities for the treatment of venous ulceration include elevating the legs above the heart (19) and compression therapy to improve ulcer healing and prevent recurrence (20-22) with a recent meta-analysis suggesting that multilayer compression therapy is superior to single-layer bandaging (23). Other options that have been studied with various degrees of success include compression sclerotherapy, echo sclerotherapy (31), ultrasound-guided foam sclerotherapy (32), skin grafting (33), superficial venous surgery (34), and sub-fascial endoscopic perforator surgery (35) and sub-fascial endoscopic perforator surgery (36) although endovenous laser therapy and vein surgery with or without skin grafting should be considered only as a final option when all other measures have failed (17). Tissue-engineered skin equivalent (recently approved by the U.S. Food and Drug Administration) is an exciting development in the treatment of venous ulcer (37) and granulocyte-macrophage colony stimulating factor (GMCSF), has proved to be effective both intralesionally and topically in two randomized, double-blind, placebo-controlled studies (38-41). Currently, keratinocyte growth factor-2 (KGF-2) is under investigation to assess its safety and efficacy in humans (42). Medication with aspirin (24), pentoxifylline (25-28) and a methylxanthine derivative has been found effective (29). Flavonoid drugs have been used in the management of venous disease and their effects upon microcirculation studied. Micronized purified flavonoid fraction (MPFF) has been used in animal models and has shown efficacy in modulating leukocyte adhesion and preventing endothelial damage.(30) Human patients with venous disease have shown similar biochemical effects which may explain the efficacy of this novel treatment in the management of symptoms, edema and modification of venous leg ulcer healing (18). MPFF compounds are believed to act in the macrocirculation, improving venous tone as well as in the microcirculation decreasing capillary hyperpermeability (46). This inhibition is linked to a significant decrease in plasma levels of endothelial adhesion molecules (VCAM-1 and ICAM-1). The lymphatic system is improved also due to the lymphagogue activity (47) modulating leukocyte adhesion and preventing endothelial damage, thereby improving symptoms of chronic venous ulceration (48,49). Silvercel, a hydro-alginate is a highly-absorbent material that maintains an optimal antimicrobial and moist wound healing environment in medium to heavy exuding wounds (50,51) . When in contact there is an exchange of sodium ions from the wound fluid with calcium ions on the alginate. This action gives the alginate its high absorbent properties, superior to a hydrofibre dressing (52,53), creating a warm, moist environment for wound healing and allowing non-traumatic removal of the dressing (54), although some (personal comment) feel that the silver dressing is unsuitable for painful ulcers and that the excessively moist environment produced by it and by Nugel actually delays healing by increasing maceration. However, that this one reported case healed in four weeks after failures over six years does suggest that the Silvercel/Nugel combination probably played at least some part in the success of the quadruple treatment.

Quadruple therapy is relatively expensive but the cost-effectiveness is governed by other considerations. The healing time of venous lower limb ulcers is significantly reduced with quadruple therapy and for this reason combination therapy is recommended for non-healing chronic venous ulcers that are resistant to other classic treatments.