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DOI: 10.1111/j.1610-0387.2008.06674.x Academy 389

© The Authors • Journal compilation © Blackwell Verlag, Berlin • JDDG • 1610-0379/2008/0605-0389 JDDG | 5˙2008 (Band 6)

CME

Current therapeutic options of chronic leg ulcers

Regina Renner, Jan C. SimonDepartment of Dermatology Venerology and Allergology, University of Leipzig A.ö.R

SummaryWound treatment is continually becoming more complex and difficult. In thefollowing review, we focus on the different options of wound debridement,stimulation of granulation tissue, different wound dressings, and therapeuticstrategies in hard-to-heal-wounds. We also present some future treatmentoptions for chronic wounds.

IntroductionWound therapy and chronic wounds have become a growing concern in research andthe health care industry in recent years, adding to the complexity and difficulty ofwound therapy. The definition of a chronic wound varies widely and ranges from6–12 weeks. The number of people affected by chronic wounds is on the rise, part-ly as a result of population aging. In Germany, chronic wounds affect roughly 2–4million people [1], although a lack of studies makes it difficult to estimate the exactnumber. Venous leg ulcers, which account for 60–80 % of all chronic ulcers, are themost common cause of wounds that fail to heal spontaneously (arterial ulcerations15–30 %, mixed arteriovenous ulcerations about 10 %, and other forms about10 %). According to the 2003 Bonn Vein Study, about 0.7 % of the German popu-lation has an active or healed venous leg ulcer [2]. As these figures show, chronicwounds are an important socio-economic concern for the health care system. In the discussion of modern wound care presented in this article, we focus on con-servative therapy of chronic leg ulcers, appropriate wound debridement and careaccording to healing phase, and future treatment options.

Physiological wound healingWound healing involves the closure of a defect by repair, regeneration, and scar for-mation. Under normal circumstances, trauma is followed by activation of a clottingcascade with subsequent release of growth factors and initiation of inflammation.During the exudative and later resorption phase, cell debris and microorganisms arecleared away and fibroblasts and endothelial cells migrate to the wound area. Inresponse to growth stimulation, fibroblast proliferation, angiogenesis, and new for-mation of the extracellular matrix begin. Granulation tissue forms. Wound contrac-tion and epithelization of the newly-formed granulation tissue commence, while pro-liferation of connective tissue decreases. After epithelization, replacement tissue con-solidates and begins to form stable scar tissue. When wound healing is impaired, this process comes to a halt. The longer the delay,the less ability the wound has to recover on its own. It is therefore essential to iden-

Keywords• modern wound therapy• wound treatment• chronic wounds

JDDG; 2008 • 6:389–401 Submitted: 17•10•2007| Accepted: 19•12•2007

Exudative phase – inflammation

Proliferative phase – granulation

Repair phase – epithelization

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tify the source of the delay, and if possible to eliminate it while simultaneously re-stimulating healing by creating a suitable wound milieu.

DiagnosisIn any long-standing non-healing wound, proper diagnosis is essential to ensuringadequate healing. It should be recalled that a chronic wound is merely a symptomand not a diagnosis. Identification of the cause of the wound is vital. Possible causesvary and include chronic venous insufficiency (CVI), peripheral arterial occlusivedisease (PAOD), neoplasias, metabolic disorders (diabetes mellitus), vasculitides,infections, or pyoderma gangrenosum. Important studies in diagnosing non-healingwounds include: directional Doppler or duplex ultrasound of arteries and veins inpatients with suspected vascular disorder; measurement of ankle-brachial index; abiopsy from the wound margin and surrounding tissue in suspected neoplasia or vas-culitides; evaluation of sensory and motor function in potential pressure ulcers; andchemical laboratory tests to rule out iron or zinc deficiency, malnutrition, diabetesmellitus, clotting anomalies, and neoplasias of the bone marrow. In patients withclinical signs of infection, bacteriological smears should be taken and antibiotic sen-sitivity determined. Microbiological screening for methicillin-resistant Staphylococcusaureus strains (MRSA) is advisable every three to six months. Samples should main-ly be taken directly from the ulcer. If the ulcer is positive for MRSA, additionalsmears should be obtained from the nasal vestibule and possibly the throat. Measuresshould be taken to eradicate infection according to applicable hygiene guidelines,such as administration of mupirocin nasal ointment 3 x daily for 5 days. The diag-nostic approach to leg ulcers has been described in detail elsewhere [3].Complementary diagnostic and treatment measures in chronic wounds include aller-gy testing if there is surrounding dermatitis, optimization of pain therapy, andadministering a tetanus booster. An overview of recommended and supplementaryexaminations is provided in Table 1. It is not always possible to eliminate the source of impaired wound healing. Aidingthe healing process with a suitable topical therapy is therefore also an integral part ofwound care.

Wound irrigation and antisepticsFor wound irrigation, the optimal agent is a physiological solution that is sterile,non-resorbable, colorless, non-irritating, and painless. Agents that meet these criteriainclude Ringer solution and physiological 0.9% saline. Antiseptics used in chronic wounds should be colorless so as to allow assessment ofthe wound during therapy. Wound antiseptics should encompass the entire bacterialspectrum. They should not lead to resistance or trigger skin reactions or contact aller-gies. Selected agents should have only a minimally inhibitory effect on wound heal-ing. Octenidine-based antiseptics meet these criteria. Although polihexanide solu-tions (0.02 % or 0.04 %) are not officially antiseptics, since they provide good tissuepenetration, selectively damage bacterial cell membranes, and are well-tolerated, theymay be recommended for chronic wounds [4]. Povidone iodine should only be usedin chronic wounds if there is no alternative. Povidone iodine is rapidly inactivated

Table 1: Diagnosis of a leg ulcer (overview).

History + clinical evaluation Basic diagnostic tests Additional diagnostic tests

• Family history• Risk factors (number of pregnancies,

standing job, limited ambulation)?• Accompanying disease (diabetes

mellitus, cardiac insufficiency,rheumatologic disease,polyneuropathy)

• Directional Doppler ultrasound +functional tests (light-reflectionrheography or photoplethysmogra-phy with a tourniquet)

• Possible biopsy in patients withclinical suspicion of e.g. neoplasia,vasculitis

• Microbiological testing

• Duplex / Phlebography• Thrombophilia test• Exclude malnutrition• Allergy tests• Check tetanus vaccination• Pain management

Important studies in diagnosing non-healing wounds include: directionalDoppler or duplex ultrasound a biop-sy from the wound margin, neurolo-gical and chemical laboratory tests.

Complementary measures in chronicwounds include allergy testingoptimization of pain therapy, andadministering a tetanus booster.

Antiseptics used in chronic woundsshould be colorless. Wound antisep-tics should encompass the entirebacterial spectrum. They should notlead to resistance or trigger contactallergies. Selected agents should haveonly a minimally inhibitory effect onwound healing.

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by wound debris proteins, can cause sensitization, and if used for longer periods orat high concentrations can inhibit wound healing. It also colors the wound, compli-cating assessment. Another antimicrobial agent is silver. The majority of silver-based dressings andpreparations release silver in the form dissolved salts or nanocrystalline silver aftercontact with liquid such as wound fluid or exudate. Silver may be combined withactivated charcoal which filters the exudate absorbing toxins and reducing odor. Thereleased silver ions have a broad spectrum of antimicrobial and antimycotic action invitro. [5]. Our own clinical experience, as well as numerous case reports and random-ized clinical trials [6, 7] have shown that these findings also apply to in vivo situa-tions in patients with critical or clinically severe bacterial colonization, even with dif-ficult infections such as MRSA. Nevertheless, at present general evidence is still lack-ing on the superiority of silver-containing dressings [8]. In general, antiseptics should only be used in wounds with colonization or infectionand not in contaminated wounds as long-term use can inhibit healing despite other-wise good tolerability [4].

Wound debridement Methods of wound debridement include autolytic, surgical, biosurgical, mechanical,or enzymatic debridement. Enzymatic wound debridement is generally not advisablegiven the unfavorable risk-to-benefit ratio. This method requires frequent dressingchanges, and wound margins can become irritated if there is contact with healthyskin. Enzymatic wound debridement should therefore only be used for brief inter-vals, in wounds with soft, easily removable fibrin coatings, or together with surgicaldebridement [9].Autolytic wound debridement is best achieved with a hydrogel dressing, preferablyan occlusive one (e.g., application of a hydrogel sheet for 1–3 days). The high watercontent in (60–95 %) in hydrogel dressings leads to swelling of necrotic tissue andnonviable fibrin coatings. In wounds with minimal fibrin, hydrogels may be com-bined with an exudate-absorbing dressing so that already detached cell detritus canbe immediately absorbed; this also facilitates surgical debridement when the dressingis later changed. Hydrogel dressings can be adapted to the amount of wound exudateto provide an optimal moist environment at the wound surface. It is important thathydrogels never be used alone, but always in conjunction with an occlusive dressingor one that absorbs wound exudate. For infected wounds, it is advisable to use a com-bination of silver-based topical therapies. Hydrogel dressings should not be used inbleeding wounds, fistula, or body cavities. One of the major advantages of hydrogelsis less frequent dressing changes since they are able to provide a uniformly moist envi-ronment at the wound surface over a longer period of time. Sensitization is possible,usually in response to the additive propylene glycol.Biosurgical debridement (maggot therapy) refers to debridement with sterile fly lar-vae, e.g., from the species Lucilia sericata, necrophages whose saliva contains enzymesthat lyse necrotic tissue and selectively remove nonviable tissue by ingestion. Themaggots are classified as a prescription drug and are obtained in gauze packages or asfree-roaming larvae. 10–15 larvae/cm2 are applied to the wound surface. If free-roaming larvae are used, they should be covered to prevent escape. Larvae remain for1–4 days in the wound, during which time they can grow to nearly ten times theiroriginal size. Treatment should be repeated if initial debridement is inadequate. Major advantages of maggot therapy include its high degree of effectiveness, theselectivity of the larvae for nonviable tissue, and an often nearly painless and tissue-sparing removal of necrotic tissue by the extracorporeal digestion mediated by pro-tease. In addition, there is evidence of antimicrobial action of the larval secretionsagainst Gram-positive bacteria, including MRSA [10] as well as of fibroblast-stimu-lating effects with improved extracellular matrix remodeling [11]. Complicationsinclude bleeding if treatment is too long or if very superficial vessels are present inthe treated area.Indications for maggot therapy include ulcers with dry, firmly adherent necrotic tis-sue or a heavy fibrin coating which are especially painful and difficult to manage withsurgical debridement. Contraindications for maggot therapy are heavy bleeding in

The released silver ions have a broadspectrum of antimicrobial andantimycotic action in vitro.

Methods of wound debridementinclude autolytic, surgical, biosurgical,mechanical, or enzymatic debride-ment.

Hydrogel dressings are the bestmethod of autolytic wound debride-ment.

Hydrogel dressings provide an opti-mal moist environment at the woundsurface. It is important that hydrogelsshould be used in conjunction withan occlusive dressing.

Biosurgical debridement refers to amethod of debridement that usessterile fly larvae.

Major advantages of maggot therapyinclude its high degree of effective-ness, the selectivity of the larvae fornonviable tissue, and the often virtual-ly painless removal of necrotic tissue.

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the wound area, close proximity to large blood vessels, and wounds that are difficultto reach or are in contact with large body cavities or internal organs.Surgical debridement using a ring curette, scalpel, forceps, or a sharp spoon has beenaugmented by procedures using a water jet or ultrasound. In water-jet dissection,wound debridement is achieved by a high-pressure jet of water. High-pressure water-jet dissection produces a cutting effect and thus achieves highly precise wounddebridement of removal of fibrin and necrotic tissue. At low pressures, the water-jetis used for irrigation only. Local or infiltration anesthesia is usually needed. Usuallycomplete debridement can be achieved in a single session. In ultrasound debridement (25 kHz, output power 35–40 W/cm2) the main mech-anism at work is cavitation. Cavitation refers to the formation and then oscillationor implosion of small bubbles in a fluid owing to ultrasound-induced compressiveand tensile forces. Implosive collapse, in particular, can produce microflows and pres-sure gradients through which can achieve selective necronectomy and reduce bacter-ial colonization [9]. Both procedures are relatively technically complex and time-con-suming. Contamination of surrounding areas by mist droplets is possible.

Phase-appropriate wound careThere stages in wound healing – inflammation, granulation, and epithelization –overlap to a certain degree and are often inseparable in everyday clinical practice.Nevertheless, one or two forms of regeneration usually dominate. Correct identifica-tion of the healing phase and selection of an optimal wound dressing are essential totherapy (Table 2). Various models proposed to describe wound healing may serve as a basis for deter-mining therapy. One such model is based on the TIME principle [12], which definesfour target structures that should be assessed and addressed in chronic wound thera-py. T stands for time, I for inflammation or infection, M for moisture, and E foredge. These components form the basis for diagnosis and therapy of chronic wounds.It is important that the wound dressing maintain an optimal moist wound environ-ment by being adequately absorbent so as to drain exudate, tissue debris, and bacte-ria. It should also protect the area from external factors (e.g., pressure, friction, andbacteria) or loss of heat. Finally, the dressing should be well tolerated, that is, itshould have low allergy potential and allow for atraumatic removal.The cost-effectiveness of modern wound dressings lies in reducing the need to changedressings, which in turn reduces the number of secondary dressings as well as relatedpersonnel costs for physician/nurse care. Dressings are generally left in place for 2–4days.A systematic analysis of controlled studies has shown that the choice of an appropri-ate wound dressing – based on wound-healing phase and exudate – can improvehealing in chronic venous insufficiency beyond the results of correctly performed

Table 2: Wound dressings by main indications and potential interactions.

Debridement Granulation Epithelization

Hydrogels Hydropolymers Hydropolymers (thin)

Alginates / Hydrofibers Hydrocolloids Hydrocolloids (thin)

Activated charcoal Alginates Hydrofibers Hydrogel dressing

Enzymatic wounddebridement

Collagen Gauze

Hyaluronic acid

Surgical debridement using a ringcurette, scalpel, forceps, or a sharpspoon has been augmented by pro-cedures using a water jet or ultra-sound.

There is a degree of overlap betweenstages of wound healing – inflamma-tion, granulation, and epithelization.

Wound dressings should not onlymaintain an optimal moist woundenvironment, but should have lowallergy potential.

The cost-effectiveness of modernwound dressings lies in reducing theneed to change dressings. Dressingsare generally left in place for 2–4 days.

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compression and standard wound care [13]. Unfortunately, there are as yet no stan-dardized evidence-based studies demonstrating the superiority of one dressing overanother in terms of healing [14]. Treatment options for various wound situations aredescribed in Table 3.

GranulationDressings which are suitable for stimulating granulation include alginate, hydrofiber,hydrocolloid, and hydropolymer dressing. Vacuum therapy also promotes granula-tion.

AlginatesAlginate dressings are derived from seaweed. The main component is calcium algi-nate. Calcium alginate fibers absorb sodium-rich wound exudate, transforming itinto soluble sodium alginate while giving off calcium ions. This leads to formationof fibrous gel. Depending on the product, the exudate can be distributed horizontal-ly or vertically over the wound edge. Unfortunately, the exudate is partly releasedagain under compression. In wounds with heavy drainage, alginates may be com-bined with polyurethane foam. For wounds that tend to be drier, alginate dressingsmay be moistened. An advantage of alginates is that the lacking adhesive layer aroundthe margin means there is almost no irritation to the wound edge. They are thus pre-ferred in wounds with surrounding eczema. Alginates are also suitable for packingdeep and gaping wounds.

Hydrofibers/aquafibersHydrofiber dressings are primarily made up of sodium carboxymethylcellulose. Likealginates, they are highly absorbent and are also very similar to alginates in terms oftheir properties and use. Hydrofibers differ from alginates in that they form a soft gelupon contact with fluid, which can be removed without leaving any residue. The gelarises through vertical wicking only in the moist wound, thus avoiding maceration atthe wound edges.

HydrocolloidsHydrocolloids have a self-adhesive surface which contains absorbent particles. Themost common are carboxymethylcellulose, pectin, or gelatin. Beneath this surface,hydrocolloid dressings consist of a polyurethane film or foam. After absorbingwound exudate, a viscous gel forms which maintains the moist environment of thewound without adhering to its base. This allows formation of a blister beneath thedressing. When the blister reaches the wound edge, the dressing must be changed.The color and sweet odor of the gelled exudate may cause it to be mistaken for bac-terial colonization or infection. Hydrocolloid dressings are highly occlusive and should only be used in wounds with-out signs of fibrin, necrosis, or clinical infection. Otherwise, massive bacterial prolif-eration can occur under the dressing. The use of hydrocolloid dressings in largerwounds is limited as the seal with the wound edge is often inadequate, allowinggelled exudate to leak or the dressing to slip. Hydrocolloid dressings should extend2–3 cm over the wound edge.

Foams/hydropolymersPolyurethane foam dressings absorb exudate without changing size or shape. Theyshould extend 1.5–2 cm over the wound edge. Exudate is absorbed by means of cap-illary force via pores in the foam. The absorbed moisture is usually not released undercompression. Unlike polyurethane foam dressings, hydropolymer dressings expand asthey absorb fluid, conforming to the wound surface. They are thus appropriate foruse in more heavily exuding wounds.Polyurethane foams and hydropolymers can be readily combined with gels, alginates,and dressings consisting of collagen or hyaluronic acid.

Vacuum therapyVacuum therapy can assist stimulation of wound granulation and neovascularization.In animal models, vacuum therapy has been shown to increase granulation by up to

Dressings which are suitable for stimu-lating granulation include alginate,hydrofiber,hydrocolloid,and hydropoly-mer dressing.

After absorbing the exudate, alginatesare transformed into a fibrous gel.

Hydrofiber dressings are highlyabsorbent and are very similar to algi-nates in terms of their properties anduse.

After absorbing wound exudatehydrocolloids a viscous gel whichmaintains the moist environment ofthe wound without adhering to itsbase.

Hydrocolloid dressings are highlyocclusive and should only be used inwounds without signs of fibrin, necro-sis, or clinical infection.

Polyurethane foam dressings areappropriate for use in more heavilyexuding wounds.

Vacuum therapy can assist stimula-tion of wound granulation and neo-vascularization.

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Table 3: Examples of use of various treatment modalities depending on condition of the wound.

Wound stage Characteristics Possible wound dressings

Special features

NecrosisBlack

• Wound is often dryor covered with dry-ing fibrin

• Firmly-attached blacknecrotic tissue

• Possibly autolyticdebridement withhydrogels or anti-septic dressings

• Important: Deve-lopment of moistgangrene

• Requires surgicaldebridement

• Possibly biosurgery

• Important:Risk of infection

Necrotic tissue andfibrin, possibly granulationBlack, yellow, andpossibly red

• Wound is damp,usually fetor

• Firmly-attached yellowish fibrin coatings or green-gray bacterialsuperinfection

• Moist antisepticdressings

• Hydrogel and sil-ver/activated char-coal dressings

• Hydrogel and hydrofiberdressings with silver

• Requires surgicaldebridement

• Possibly biosur-gery

• Important:Risk of infection

Fibrin coatings andgranulation

Yellow and red

• Possibly a slight yel-lowish fibrin coating

• Red or pink woundbase

• Polyurethane foam• Moistened alginates• Possibly with a

hydrogel• Possibly hydrofiber

dressing with silver(wound cavity)

• Possibly vacuumtherapy

SclerosisYellow and white

• Limited amount of fibrin

• Wound base is non-reactive, sclerotic with-out granulation tissue

• Collagen plus po-lyurethane foam

• Hydrocolloids• Possibly hydrogel

• Possibly ulcersurgery

Granulation

Red

• No fibrin coatings,granulation tissue

• Red, well-vasculari-zed wound base

• Polyurethane foam• Hydrocolloids for

smaller wounds

• Possible vacuumtherapy

Granulation andepithelium

Red and pink

• Epithelial islandsthat usually extendfrom the margin inward

• Thin polyurethanefoam dressing

• Gauze• Thin hydrocolloid

dressing

Wound edge

Maceration, erosion,eczema

• Maceration/erosion:surrounding skin:deep red, possiblywhitish softening

• Eczema: Scales around wound withpoorly-defined redborders or rednessalong the margins ofdressing adhesive, often with pruritus

• Silver/activated charcoal dressing

• Hydrofiberdressing with silver

• Alginates• Non-adhesive

polyurethane foam• Gauze

• Wound marginprotection

• Treat woundmargins with local steroids ifnecessary

103.4% compared with saline-soaked compresses, with the best stimulation of gran-ulation at an intermittent negative pressure of –125 mmHg. Vacuum therapy mayalso be used in wounds with critical colonization. Efficacy is reportedly improved byintermittent instillation of antiseptic or antibiotic solutions, known as vacuum-assist-ed closure with instillation (for a comprehensive overview of vacuum therapy see[15]).

Epithelization Thin polyurethane or hydrocolloid foams are suitable for epithelization.Hypergranulation should be avoided. Hydrogel dressings may also be used in mini-mally exuding wounds. The gel pads are transparent and thus allow evaluation of thewound throughout the course of healing. Impregnated gauze bandages may be usedfor erosions. A special coating or specific properties of the materials (e.g., silcone)prevent adherence to the wound. A finely-woven gauze mesh should be chosen toavoid ingrowth of granulation tissue or epithelium. Both ensure atraumatic dressingchanges.

Autologous keratinocyte transplantation and split-skin graftsAnother option for wound closure is surgical therapy with autologous split-skingrafting or various non-invasive tissue replacement methods. Defect coverage with an autologous split-skin graft involves taking a portion of skinmeasuring about 0.4 mm with a dermatome from the back of the patient’s head orthe thigh. Split-skin grafts can also be used to treat large wound defects by attachinga mesh to the outer wound margin. Split-skin grafting has several advantages: it is anuncomplicated surgical method for rapid defect coverage (with related advantagessuch as an only briefly opened portal of entry for pathogens), there is a lot of expe-rience with the procedure, and it can be readily combined with other procedures suchas subsequent vacuum therapy for fixation of the graft or pre-procedure ulcer shav-ing and/or fasciectomy. In ulcer shaving, the wound is débrided at an angle until thehealthy ulcer base is reached. Disadvantages of split-skin grafting include the creationof a new wound defect which may also have difficulty healing. The surgical proce-dure often requires a hospital stay and in multi-morbid patients related intraopera-tive and postoperative risks. It is not within the scope of the present article, which focuses on conservative woundcare, to describe additional operative measures or discuss them in greater detail. An example of a non-invasive tissue replacement procedure is autologous ker-atinocyte grafting for an epidermal equivalent. Depending on the size of the wound,45-290 anagen hairs are removed by epilation from the scalp hair on the side of thepatient’s head. In an organotypic culture, an epidermal equivalent is cultivated invitro from the cells of the outer root sheath of the hair follicle for about 4 weeks. Theproliferation potential of cells of the outer root sheath is not dependant on donorage, which is an important factor given the average age of people with chronic ulcers.When they are ready, the epidermal equivalents are roughly the size of a 1-cent coin.Similar to the human epidermis, the silicone disks (0.8 cm2) have multiple layers ofkeratinocytes on their underside. Currently, the primary indications for this proce-dure are chronic venous leg ulcers or mixed arteriovenous ulcerations. This methodhas the advantage of being able to be performed as an outpatient procedure. It is alsopainless and does not involve complications, even in older and multi-morbidpatients. Disadvantages include the need for the wound to be very well-conditionedprior to therapy, the necessity of a two-stage procedure and thus a delay of about 4weeks, and the initially higher costs.

Hard-to-heal woundsIf adequate granulation cannot be achieved using the modern wound therapiesdescribed above, additional wound dressings and aids such as collagen, protease-modulating topical treatments (collagen and hydrated cellulose), or hyaluronic acidmay be used. The hydrophilic properties of hyaluronic acid can help achieve an opti-mal moist environment at the wound surface. The use of collagen can stimulate for-mation and organization of the body’s own collagen in the wound area and help formbetter scar tissue. Protease-modulating topical therapies can irreversibly deactivate

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Thin polyurethane or hydrocolloidfoams are suitable for epithelization.

Impregnated gauze bandages may beused for erosions.

Another option for wound closure issurgical therapy with autologoussplit-skin grafting or various non-invasive tissue replacement methods.

In hard-to-heal wounds additionalaids such as collagen, protease-modulating topical treatments, orhyaluronic acid may be used.

excess protease in the wound environment while protecting endogenous growth fac-tors from proteolysis [16].Along with reduced bacterial colonization, modulation of pH levels has a directimpact on wound healing. Chronic wounds usually have alkaline pH levels, whileacute or healing wounds have an acidic pH. The mechanism of action is attributedto decreased enzyme activities of matrix metalloproteinases (MMPs) and other pro-teases [17]. There are already a few products on the market that act by modulatingpH levels [18]. Electrotaxis is another new aspect of therapy that allows regulation of an impairedwound healing cascade. Experimental studies have shown that the direction of thebody’s wound-inducing electric field can regulate the migration inflammatory cells,endothelial cells, fibroblasts, and keratinocytes and influence pH and bacterial colo-nization influenced [19]. Current clinical practice already includes treatment proce-dures based on this principle [20].

Infected wounds and critical colonization The presence of bacteria in a chronic wound does not influence healing so long ascolonization does not lead to clinically-relevant infection (with redness, swelling,warmth, or an increase in inflammatory parameters) or detection of more than fourbacterial species. If there is bacterial colonization with more than four differentspecies, healing of a venous leg ulcer is impaired, as is also the case with the forma-tion of biofilms in the wound base [21]. Reduction and/or elimination of bacterialcolonization is thus imperative for wound healing. There is also an increase world-wide in contamination of chronic wounds with problem bacteria MRSA,Pseudomonas aeruginosa, and vancomycin-resistant enterococci (VRE).In addition to the previously mentioned antiseptics, biosurgical methods, and sys-temic antibiotics necessary in infected wounds, nearly all wound dressings for treat-ing ulcers with critical colonization are also available with elementary silver or silvercomplexes, as already described under ‘‘wound antiseptics.’’ Occlusive dressings suchas hydrocolloids should be avoided in ulcers with critical colonization.Future treatment options for infected ulcers and those with critical colonization (e.g.,with problem bacteria such as MRSA) may include induction or administration ofantimicrobial peptides, pH modulation, use of bacteriophages, and photodynamictherapy [17, 22, 23].

Protection of the wound margin and epithelial islandIf an optimal wound dressing is used, there is no need for special protection of thewound margins since the dressing already regulates wound moisture. Problem wounds can occur, however, with periods of massive exudation resulting inmaceration of existing or newly formed epithelial islands or bridges at the surface ofthe wound. Irritation can arise from stool, urine, or dressing materials such as usedin vacuum therapy, or from other mechanical stresses. Epithelial islands are pieces ofskin without contact to the wound margin, while epithelial bridges project from theedge into the wound and are connected to the margin at the base. Any epithelialislands or bridges, as well as the wound margin itself, are potential sites of epidermalregeneration. Application of a transparent water-repellant polymer film to epithelialislands and wound margins significantly reduces any irritating, toxic effects on theepithelium. Maintaining epithelial islands ultimately promotes more rapid healing ofthe wound [24]. Zinc pastes and similar zinc-containing preparations also counter-act maceration of the skin. The low cost of these preparations is an advantage.Disadvantages include drying and irritation of the wound edge from excessive appli-cation or removal of the paste as well as reduced adhesiveness of wound dressings.The whitish discoloration also makes it more difficult to accurately assess the woundmargin.Wound margins often need additional care as they may dry out or wound exudatemay accumulate under the dressing. Either of these situations can promote irritanteczema or infection due to microtrauma. It is well known that patients with chronicwounds often develop type IV allergy. When selecting an appropriate topical thera-py, care should be taken to use as few substances as possible and to choose hypoaller-genic remedies without any added fragrances. About 9 % of patients with leg ulcers

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Modulation of pH has a direct influ-ence on wound healing.

Experimental studies have shownthat electrotaxis can regulate themigration of inflammatory cells,endothelial cells, fibroblasts, and ker-atinocytes.

The presence of bacteria in a chronicwound does not necessarily influencehealing.

There is an increase worldwide in contamination of chronic woundswith problem bacteria MRSA,Pseudomonas aeruginosa, and van-comycin-resistant enterococci (VRE).In addition to the previously-men-tioned methods, nearly all wounddressings for ulcers with criticalcolonization are also available withelementary silver or silver complexes.

Application of a transparent water-repellant polymer film to epithelialislands and wound margins signifi-cantly reduces any irritating, toxiceffects on the epithelium.

Wound margins often require addi-tional care.When selecting an appropriate topicaltherapy, care should be taken to use asfew substances as possible and tochoose hypoallergenic remedies with-out any added fragrances.

have type IV allergy. The use of phytotherapeutics should generally be avoided giventheir high allergenic potential. Epicutaneous testing is mandatory in patients withsuspected type IV allergy. Sensitization to the wound care products is also possible.Reactions have been reported to hydrocolloids and ingredients contained in adhe-sives such as pentaerythritol esters from hydrogenated rosin or colophony. Otherallergens include propylene glycol in hydrogels and PVP iodine or cadexomer iodineas antiseptic additives.

Evidence levels and recommendation gradesThe guideline ‘‘Diagnosis and Therapy of Venous Leg Ulcers’’ [3] provides recom-mendations concerning specific diagnostic and therapeutic methods. Tables 4 and 5,which list evidence levels and recommendation grades respectively, are based on theguideline and serve as a rough guide for the therapies cited in the present article.

Future directionsOur understanding of wound healing has increased considerably in recent years. It isnow clear that several cytokines are responsible for forming a complex regulatory ele-ment in wound healing. These include keratinocyte growth factor (KGF), vascularendothelial growth factor (VEGF), and transforming growth factor-� (TGF-�).VEGF-A, which is responsible for angiogenesis in wounds, has been shown in chron-ic wounds to undergo proteolytic degradation, mainly by plasmin, a serine pro-teinase. This has led to a new approach involving the creation of plasmin-resistantVEGF-A mutants which may be used for therapy [25]. Other therapeutic notions involve influencing the larger numbers of MMPs found inwound exudate. If uncontrolled, these lead to increased degradation of cytokines,growth factors, and structural proteins, which in turn can no longer be active inwound healing. A complementary therapeutic approach is reduction of the often elevated levels ofinflammatory mediators in wound exudate such as interleukin-1, interleukin-6, ortumor necrosis factor (TNF) [26]. Given developments in stem cell research, it is also conceivable that mesenchymal,endothelial, or multipotential cells could be mobilized from the bone marrow andused in wound therapy. It is also now recognized that wound healing or its impairment might be influencedby microRNAs. MicroRNAs are short nucleotides that regulate the expression ofgene products by inhibiting translation or transcription. VEGF production in partic-ular seems to be affected, and thus angiogenesis could be regulated. During specificphases of wound healing, there is also a change in specific microRNAs, which opensup completely new diagnostic and therapeutic possibilities [27].

ConclusionsThe most important step in chronic wound therapy is to tailor treatment to the causeand etiology of the wound whenever possible. Appropriate measures should not beneglected, including surgical methods (e.g., stenting in PAOD or vein stripping),optimization of compression therapy in chronic venous insufficiency (CVI), reduc-ing lymphedema with physiotherapy, relief of pressure in diabetic foot and decubi-tus, and simple gait training in PAOD and CVI. In elderly patients and thosedependent on help for eating, malnutrition can result from an improper or inade-quate diet. Resulting iron, zinc, or protein deficiency can have an unfavorable influ-ence on wound healing. Prudent use of modern wound therapy methods also improves management ofchronic wounds. The goal need not always be more rapid healing, but rather can also encompass areduction in pain or improved quality of life.With the development of guidelines and the results of controlled studies, includingthose taking pharmaco-economic factors into consideration, improvements will con-tinue to be made in wound care.

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The most important step in chronicwound therapy is to tailor treatmentto the cause and etiology of thewound.

In elderly patients and those depend-ent on help for eating, malnutritioncan occur.

The goal need not always be healing,but rather can also encompass animproved quality of life.

Epicutaneous testing is mandatory inpatients with suspected type IV allergy.

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Table 4: Evidence levels for selected diagnostic and therapeutic approaches.

Keyword Evidence level Recommendationgrade

Tetanus vaccination D1 A

Histological analysis D2 B

Malnutrition D3 C

Surgical debridement T1a A

Zinc paste T4 C

Antiseptic use K1 A

Local therapy / modern wounddressings

T1a A

Vacuum therapy (leg ulcer) Ib A–B

Varices surgery (epifascial) T2b B

Keratinocyte transplantation /epidermal equivalent

T1a A

Table 5: Legends for Table 4.

Level Recommendation Definition

Therapy (excerpt)

T 1a AMeta-analysis, systematic review ofrandomized controlled trials (RCT), or “mega-trial”

T 2b B Case control study

Causality (excerpt)

K1 A RCT

Diagnosis (excerpt)

D1 AIndependent, blind assessment, consecutivepatients, appropriate spectrum

D2 BAs above, but not meeting criteria “consecutivepatients and/or appropriate spectrum”

D3 B–C Other studies compared with gold standard

Evidence level and recommendation grade based on Oxford Centre of Evidence-Based Medicine Classification (excerpt)

Ib A Evidence from appropriate planned RCT

Conflict of interestNone.

Correspondence toDr. R. RennerKlinik für Dermatologie, Venerologie und AllergologiePhilipp-Rosenthal-Straße 23–25D-04103 LeipzigTel.: +49-341-97-18600Fax: +49-341-97-18609E-mail: regina.renner@medizin.uni-leipzig.de

References1 Körber A, Kohaus S, Geisheimer M, Grabbe S, Dissemond J. Allergic contact dermati-

tis from a hydrocolloid dressing due to colophony sensitization. Hautarzt 2006; 57:242–245.

2 Rabe E, Pannier-Fischer F, Bromen K, Schuldt K, Stang A, Poncar C, Wittenhorst M,Bock E, Weber S, Jöckel KH. Bonner Venenstudie der Deutschen Gesellschaft fürPhlebologie. Phlebologie 2003; 32: 1–14.

3 Gallenkemper G, Bulling BJ, Kahle B, Klüken N, Lehnert W, Rabe E, Schwahn-Schreiber C. Leitlinien zur Diagnostik und Therapie des Ulcus cruris venosum.Phlebol 1996; 25: 254–258.

4 Kramer A, Daeschlein G, Kammerlander G, Andriessen A, Aspöck C, Bergemann R,Eberlein T, Gerngross H et al. Konsensusempfehlung zur Auswahl von Wirkstoffen fürdie Wundantiseptik. ZfW 2004; 3: 110–120.

5 Lansdown AB. Silver 1: its antibacterial properties and mechanism of action. J WoundCare 2002; 11: 125–130.

6 Jørgensen B, Price P, Andersen KE, Gottrup F, Bech-Thomsen N, Scanlon E, KirsnerR, Rheinen H, Roed-Petersen J, Romanelli M, Jemec G, Leaper DJ, Neumann MH,Veraart J, Coerper S, Agerslev RH, Bendz SH, Larsen JR, Sibbald RG. The silver-releasing foam dressing, Contreet Foam, promotes faster healing of critically colonisedvenous leg ulcers: a randomised, controlled trial. Int Wound J 2005; 2: 64–73.

7 Edwards-Jones V. Antimicrobial and barrier effects of silver against methicillin-resist-ant Staphylococcus aureus. J Wound Care. 2006; 15: 285–290.

8 Chambers H, Dumville JC, Cullum N. Silver treatments for leg ulcers: a systematicreview. Wound Rep Regen 2007; 15: 165–173.

9 Dissemond J, Goos M. Optionen des Debridements in der Therapie chronischerWunden. J Dtsch Dermatol Ges 2004; 2: 743–751.

10 Huberman L, Gollop N, Mumcuoglu KY, Block C, Galun R. Antibacterial propertiesof whole body extracts and haemolymph of Lucilia sericata maggots. J Wound Care2007; 16: 123–127.

11 Horobin AJ, Shakesheff KM, Pritchard DI. Promotion of human dermal fibroblastmigration, matrix remodelling and modification of fibroblast morphologie within anovel 3D model by Lucilia sericata larval secretions. J Invest Dermatol 2006; 126:1410–1418.

12 Vanscheidt W, Ukat A, Hauß F, International Wound Bed Preparation AdvisoryBoard. Systematisches Management chronischer Wunden nach dem TIME-Prinzip.MMW 2005; 147: 119–126.

13 O´Donnell TF, Lau J. A systematic review of randomized controlled trials of wounddressings for chronic venous ulcer. J Vasc Surg 2006; 44: 1118–1125.

14 Palfreyman SJ, Nelson EA, Lochiel R, Michaelis JA. Dressings for wound healingvenous leg ulcers. Cochrane Database Syst Rev 2006; 3: CD001103.

15 Renner R, Rogalski C, Friedlein H, Simon JC. Die Vakuumtherapie in derDermatologie: ein Überblick. J Dtsch Dermatol Ges 2006; 4: 468–476.

16 Cullen B, Smith R, McCulloch E, Silcock D, Morrison L. Mechanism of action ofPROMOGRAN, a protease modulating matrix, for the treatment of diabetic footulcers. Wound Repair Regen 2002; 10: 16–25.

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17 Weindorf M, Körber A, Dissemond J. pH-Werte modernen Wundauflagen und derenEinfluß auf das umgebende Milieu: Resultate einer in vitro Untersuchung. ZfW 2007;2: 92–97.

18 Greener B, Hughes AA, Bannister NP, Douglass J. Proteases and pH in chronicwounds. J Wound Care. 2005; 14: 59–61.

19 Zhao M, Song B, Pu J, Wada T, Reid B, Tai G, Wang F, Guo A, Walczysko P, Gu Y,Sasaki T, Suzuki A, Forrester JV, Bourne HR, Devreotes PN, McCaig CD, PenningerJM. Electrical signals control wound healing through phosphatidylinositol-3-OHkinase-gamma and PTEN. Nature 2006; 442: 457–460.

20 Gardner SE, Frantz RA, Schmidt FL. Effect of electrical stimulation on chronic woundhealing: a meta-analysis. Wound Repair Regen. 1999; 7: 495–503.

21 Davies CE, Hill KE, Newcombe RG, Stephens P, Wilson MJ, Harding KG, ThomasDW. A prospective study of the microbiology of chronic venous leg ulcers to reevalu-ate the clinical predictive value of tissue biopsies and swabs. Wound Rep Regen 2007;15: 17–22.

22 Dissemond J, Körber A, Lehnen M, Grabbe S. Methicillin-resistenter Staphylococcusaureus (MRSA) in chronischen Wunden: Therapeutische Optionen und Perspektiven.J Dtsch Dermatol Ges, 2005; 3: 256–262.

23 Clayton TH, Harrison PV. Photodynamic therapy for infected leg ulcers. Br JDermatol 2007; 156: 384–385.

24 Schuren J, Becker A, Sibbald RG. A liquid film-forming acrylate for peri-wound pro-tection: a systematic review and meta-analysis (3M Cavilon no-sting barrier film) IntWound J 2005; 2: 230–238.

25 Eming SA, Kaufmann J, Löhrer R, Krieg T. Chronische Wunde – Neue Wege inForschung und Therapie. Hautarzt 2007; 58: 939–944.

26 Streit M, Beleznay Z, Braathen LR. Topical application of the tumour necrosis factor-alpha antibody infliximab improves healing of chronic wounds. Int Wound J 2006; 3:171–179.

27 Shilo S, Roy S, Khanna S, Sen CK. MicroRNA in cutaneous wound healing: a newparadigm. DNA Cell Biol 2007; 26: 227–237.

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1. Welche Aussage trifft nicht zu?a) Die exsudative Phase der Wund-

heilung geht mit Auslösung einerInflammation einher.

b) In der proliferativen Phase entstehtvor allem Granulationsgewebe.

c) Eine Wundkontraktion kann ersteinsetzen, wenn dieEpithelisierung abgeschlossen ist.

d) Die Epithelisierung markiert dieEndphase der Wundheilung.

e) Oftmals befindet sich die Wundein sich überlappenden Wundhei-lungsstadien.

2. Folgende Untersuchungenwerden als sinnvolle und notwendigeDiagnostik chronischer Wunden beientsprechendem Verdacht eingesetzt.Welche Aussage ist nicht richtig?a) Anamneseerhebungb) direktionale Doppler- oder

Duplexsonographiec) Ausschluss von Mangelerscheinungend) Überprüfung des spezifischen IgE

auf topische Antibiotika e) Entnahme einer Hautprobe

3. Welche Aussage ist richtig? Zur topischen Wundantiseptik chronischer Wunden eignet sicha) Merbrominlösungb) Wasserstoffperoxidlösungc) Ethacridinlösungd) Octenidinlösunge) Brilliantgrün

4. Welche Aussage ist nicht richtig?Wundreinigung …a) erfolgt bei der autolytischen

Wundreinigung mittels Hydrogelenin Kombination mit einemabdeckenden oder sekretaufneh-menden Verband.

b) wird als erste Therapieempfehlungmittels enzymatischer Andauungdurchgeführt.

c) kann auch biochirurgisch durchLucilia-sericata-Maden erfolgen.

d) kann bei chirurgischen Débridementverfahren eine

Lokal- oder Infiltrationsanästhesienötig machen.

e) durch Biochirurgie bietet denVorteil der selektiven Entfernungavitalen Gewebes.

5. Welche Frage ist nicht richtig?Zur Anregung der Granulation eignen sich am bestena) Alginateb) Hydrofaserverbändec) Hydrokolloided) Polyurethanschaumverbändee) imprägnierte Gazen

6. Welche Antwort ist richtig? DieVakuumtherapie ...a) eignet sich vor allem zur Epitheli-

sierung einer Wunde.b) bewirkt den besten Granulations-

reiz bei einem kontinuierlichenUnterdruck von –225 mmHg.

c) ist nicht geeignet bei bakteriell kolonisierten Wunden.

d) darf nicht bei Diabetikern eingesetzt werden.

e) kann zu Reizung oder Mazerationdes Wundrandes führen.

7. Welche Antwort ist richtig? BeiMazeration oder Ekzemen am Wundrand ...a) sollte der Wundverband optimiert

werden, ggf. auch durch die An-wendung eines wasserabweisendenPolymerfilms.

b) sollten am besten Hydrokolloide alsWundverband verwendet werden.

c) hilft eine allergologischeAbklärung nicht weiter.

d) ist die Anwendung von Glukokor-tikoiden aufgrund des Risikos einerSuperinfektion kontraindiziert.

e) ist die Wundheilung in keinsterWeise beeinträchtigt.

8. Welche Antwort ist richtig im Zusammenhang mit chronischenWunden?a) Die körperliche Schonung von

Patienten mit chronischen

Wunden ist wichtig, damit nichtunnötig Energie verbraucht wird,die der Wundheilung nicht mehrzur Verfügung steht.

b) Operative Verfahren zur Beseitigungmöglicher Ursachen der Wundhei-lungsstörung sind der topischenWundtherapie unterlegen.

c) Eine Malnutrition oder Mangelver-sorgung an Vitaminen oder Spuren-elementen ist in Deutschland beiPatienten mit chronischen Wundennicht anzunehmen.

d) Kolonisation der Wunde mit Bakte-rien sollte immer zum Einsatz einessystemischen Antibiotikums führen.

e) Eine Kompressionstherapie stellteine wesentliche Maßnahme zurVerbesserung der Wundheilungbei einer bestehenden chronischvenösen Insuffizienz dar.

9.Welche Aussage ist nicht richtig?Folgende Techniken eignen sich füreine Wunde während der Epitheli-sierungsphase:a) die Anwendung einer imprägnier-

ten Gaze b) dünne Hydrokolloidverbändec) operative Verfahren wie Spalthaut-

transplantationd) die Anwendung der Madentherapiee) dünne Polyurethanschäume

10. Welche Aussage ist nicht richtig?Bakteriell kolonisierte Wunden …a) rechtfertigen den Einsatz von

Antiseptika.b) lassen sich nur durch den Einsatz

systemischer Antibiotika sanieren.c) können unter ärztlicher Kontrolle

durch die Anwendung silberhaltiger Wundverbände behandelt werden.

d) sind keine absolute Kontraindika-tion für den Einsatz der Installati-onsvakuumtherapie.

e) zeigen häufig einen deutlichenFoetor und eine stärkereSekretion.

Fragen zur Zertifizierung durch die DDA

Liebe Leserinnen und Leser,der Einsendeschluss an die DDA für diese Ausgabe ist der 16. Juni 2008.Die richtige Lösung zum Thema „Diagnostik und Therapie des kutanen Lupus erythematodes“ in Heft 1 (Januar 2008) ist: 1d, 2c, 3d, 4b, 5d, 6a, 7b, 8d, 9e, 10c.Bitte verwenden Sie für Ihre Einsendung das aktuelle Formblatt auf der folgenden Seite oder aber geben Sie Ihre Lösung onlineunter http://jddg.akademie-dda.de ein.