MEZINÁRODNÍ CENTRUM KLINICKÉHO VÝZKUMU
„TVOŘÍME BUDOUCNOST MEDICÍNY“
Wound healing in
dermatology
MUDr. V. Slonková, Ph.D.
I. dermatovenerologická
klinika FN u sv. Anny
v Brně a LF MU
Definition
 Wound - a defect of skin integrity
 - acute
- chronic – secondary healing wound
without tendency to heal after 6-9 weeks
Chronic wounds
 leg ulcers
 pressure ulcers
 burns
 malignant tumours
 surgical wounds with secondary healing
 ulcers after radioth
Leg ulcers
 prevalence : 1% of adults
 incidence: in population over 50
- 0,3 to 1000 inhabitants
 chronic disease : - 60 % of ulcers heal more
than 6 months,
- 33 % heal more than 1 year
 impact on quality of life
 reccurences – 2/3 of healed leg ulcers
Etiology of leg ulcers
 75% venous
 15% arterial
 10% other
Ulcus cruris infectiosum bullous
erysipelas
Basal cell carcinoma
Squamous cell carcinoma
Pyoderma gangrenosum – AI
disease
Lymphatic ulcers
Venous leg ulcers
 75% of all leg ulcers
 pathogenesis – valvular insufficiency
 2 types:
 1) ulcus cruris varicosum – due to primary
varicose veins
 2) ulcus cruris posttromboticum – due to
deep vein thrombosis
CEAP classification
 Classification and grading of chronic
venous disease (CVD) on the basis of:
 C – clinical manifestations
 E –etiologic factors
 A – anatomic distribution of involvement
 P – pathophysiologic findings
CEAP classification of CVD
C 0 – no visible or palpable signs of CVD
C 1 – telangiectases and reticular veins
C 2 – varicose veins
C 3 - edema
C 4 – skin changes: pigmentation, eczema, lipodermatosclerosis, atrophia
blanche
C 5 - skin changes + healed ulcer
C 6 – skin changes + leg ulcer
Chronic venous disease
 Vein Consult Program (2012)
 epidemiologic study in Europe, Asia, Latin
America, 90 000 persons
 CVD – global problem
 prevalence:
 84% - including stage C0s ( symptomatic
patients without clinical signs of the
disease)
 64% - from stage C1
Chronic venous disease
 in the Czech republic - prevalence - 70%
 progressive disease
 treatment costs: 350 milion Kč
 prevalence of leg ulcers – 1-2%
 Czech Vein Program,Prakt.flebol.2012;21:1-28
C4 - pigmentation
Atrophia blanche + leg ulcers
Treatment of venous leg ulcers
 surgical
 conservative:
- local treatment
- compression
- pharmacological treatment
Wound healing - TIME
 A structured wound assessment tool in
the form of acronym
 T – tissue management
 I – inflammation, infection control
 M – moisture balance
 E – epithelization advancement
TIME – T - tissue
 debridement, wound
bed preparation
Debridement
 treatment of wound bed and wound edges
 necessary for wound healing
 reduces odour, exudation
 improves quality of life
Debridement
 autolytic
 enzymatic
 biosurgical
 mechanical
 surgical
 hydrosurgical - Versajet
 UZ
 TNP (topical negative pressure)
Autolytic debridement
 the most often used method
 semi-occlusive dressings – film dressings
- hydrocolloids
- hydrogels
 create a moist wound-dressing interface
which enhances the activity of endogenous
proteolytic enzymes within the wound
 separation of necrotic tissue from healthy
tissue
Autolytic debridement
 advantage : - selective
- painless
 disadvantage : - slow
- maceration
- odour
Enzymatic debridement
 highly selective
 enzymatic agents derived from
 proteolytic enzymes extracted from bovine
plasma or pancreas, fruit and plants such as
papain from papaya or bromelain from
pineapple
 or bacterial collagenase derived from
Clostridium histolyticum
Enzymatic debridement
 Iruxol mono - bacterial collagenase
derived from Clostridium histolyticum
( tzv. clostridiopeptidasis)
 cleaves triple helix of collagen
 selective debridement of necrotic tissue
 painless
 minimal risk of bleeding
Biosurgical debridement
 larval therapy (Maggot)
 fast and very effective method
 application of sterile fly larvae (Lucilia
sericata) to the wound
 dressing change in 2-4 days
Biosurgical debridement
 complex mechanism of action
 mechanic movement of larvae
 production of proteolytic enzymes
(collagenase, trypsin) and bactericid
substances
 ingestion of bacteria
 increase th pH of the wound – inhibitory
effect on bacterial growth
Mechanical debridement
 mechanical removement of necrotic tissue
 disadvantage –pain, traumatisation of
healthy tissue
 advantage –quick method
 sharp debridement
 debridement wet-to-dry – gause – painful
Hydrosurgical debridement
 Versajet
 pressurised water or saline
 the pressure is controlled via a handset
 the jet of fluid both cut and removes tissue
while irrigating the wound
 advantage: quick
 Disadvantage: - expenssive
- painful
TIME – I (infection)
 infection,
inflammation
control
 antiseptics
Antiseptics
 synthetic antimicrobial drugs
 they kill or inhibit microorganisms
 they are not toxic for keratinocytes
 they act non selective
 broad antimicrobial spectrum
 resistance – not often
Antiseptics
 silver
 iodine
 chlorhexidin
 honey
 polihexanid
Silver dressings
 A broad antimicrobial spectrum:
 Staphylococcus aureus, including MRSA,
VRE ( vancomycin-resistent enterococci),
Streptococcus pyogenes, Escherichia coli,
Pseudomonas aeruginosa, Klebsiella
pneumoniae
 viruses, yeasts
Silver dressings
 A variety of antimicrobial dressings
containing silver
 A silver contect and physical and chemical
properties vary greatly
 Available in various formulations:
 - flat sheets
 - combined with hydrogels, alginates,
hydrofibres
 Resistance - rare
Silver
 International consensus - 2012
 „Appropriate use of silver dressings in
wounds
 www.woundsinternational.com
 Effectivity, safety, cost-effectiveness
Iodine dressings
 a broad antimicrobial spectrum:
 G+, G- bacteria, viruses, fungi
 resistence – 0
 iodine is slowly released to the wound
 2 forms: cadexomer iodine
povidone iodine
Iodine dressings
 contraindication:
- known sensitivity to iodine
- thyroid disease
 do not exceed 3 months continuous use –
risk of systemic absorption
 available in various forms:
- ointment
- paste
- flat sheets
Chlorhexidin dressings
 a broad antimicrobial spectrum:
 G+, G- bacteria, viruses, fungi
 resistence can occur
Honey dressings
 first used in ancient Egypt - 4000 years ago
 medical-grade honey dressings developed in
the late 1990s
 a broad antimicrobial spectrum, including
MRSA and VRE
 the ability of honey to produce low levels
of hydrogen peroxide in the wound
 the provision of an acidic wound
environment (pH 3)
Honey dressings
 reduce wound odour
 promote autolytic debridement
 available in various formulations:
 flat sheets
 paste
 ointment
Honey dressings
 Contraindication:
 patients with known allergy to bee stings
 highly exudating wound – risk of
maceration
 may cause stinging sensation
Polihexanid
 Polyhexamethylene biguanide (PHMB)
 a broad antimicrobial spectrum, including
MRSA
 used in healthcare and cosmetics for many
years
 no reports of bacterial resistance to date
 no allergy
Polihexanid
 well tolerated
 contraindication:
- pregnancy – first 4 months
- dry wounds
 Prontosan – PHMB + betain
TIME – M -moisture
 moisture –
management od
exudate
Moist wound healing
 moist wound necessary for optimal
healing
 optimal hydration of the wound
 copious exudate – causes leakage,
maceration, odour, infection
 minimal exudate delays autolytic
debridement, inhibits epithelialisation and
causes pain on dressing removal
Moist wound healing
 dry wounds: hydrogels
 highly exudating wounds:
- alginates
- hydrofibres
- polyurethan foams
Hydrogels
 amorphous gels
 flat sheets -gel compresses (hydrogel +
polyurethan layer)
 a high water content (30-90%)
 rehydrates dry tissue
 promote autolytic debridement
 have a cooling effect
 are easily removed
 are comfortable and flexible
Hydrogels
 may cause eczema or irritation
 they need secondary dressing
 may be combined with:
- silver
- hyaluronic acid
Hydrofibers
 nonadherent dressings
 ability to absorb high levels of wound
exudate
 composed of sodium
carboxymethylcellulose
 form non-adherent gel in exuding wounds
 create a moist wound-dressing interface
Hydrofibers
 promote autolytic debridement
 available in varius formulations:
- flat sheets
- packing rope for cavities
- combined with silver – antimicrobial
activity
 contraindication: dry wounds
Polyurethane foam dressings
 semipermeable
 low adherent, soft, highly absorbent
 outer semipermeable membrane – allows
fluid to pass into the insulating foam
 waterproof
 gas/water vapour permeable
 impermeable to bacteria
 create a moist wound-dressing interface
Polyurethane foam dressings
 available in various formulations:
 adhesive/non-adhesive
 shaped cavity devices for cavity wounds
 shaped sacral or heel dressings
 thin
 combined with silver or PHMB –
antimicrobial activity
 combined with charcoal – reduce odour
 contraindication: dry wounds
Polyurethane foam dressings
Silicone dressings
 silicone – inert material
 atraumatic dressings
 painless dressing change
 non-adherent sheets
 polyurethane fom dressings with silicone
Alginate dressings
 Obtained from seaweed
 High absorbents
 Derived from calcium/sodium salts of
alginic acid
 On contact with wound fluid, sodium salts
in the exudate exchange with tha calcium in
the alginate dressing to form a soft gel
which maintains a moist environment
Alginate dressings
 should be cut to the shape of the wound
 hemostatic properties
 may provide pain relief
 available in various forms:
 flat sheets
 packing rope for cavities
 combined with silver or charcoal
Charcoal dressings
 active charcoal
 reduction of odour
 absorption of microorganisms and exudate
TIME – E - epithelialisation
Bioactive dressings
 indication: hard-to-heal ulcers
 20% of leg ulcers
 bad prognosis – leg ulcers larger than 10
cm2 and lasting more than 6 months
Bioactive dressings
 protease modulating dressings
 hyaluronic acid dressings
 collagen dressings
 growth factors
 skin substitutes
Matrix metalloproteinases
(MMPs)
 group of zinc-dependent endopeptidases
 produced by granulocytes, keratinocytes
and fibroblasts
 elevated protease activity in chronic
wounds
 decreased levels of TIMPs (tissue
inhibitors of MMPs)
Protease modulating dressings
 composed of collagen and ORC – oxidised
regenerated cellulose
 act by absorbing wound fluid and trapping
proteases within their structure to render
them inactive
 form a non-adherent gel which binds with
growth factors protecting them from
degradation by MMPs
Oxidized celullose
Hyaluronic acid
 main part of extracellular matrix
 glucosaminoglycan
 hygroscopic – skin hydration
 antioxidant
Hyaluronic acid
 accelerates wound healing ( acute and
chronic wounds)
 reduces scarring
Growth factors
 Regranex - recombinant PDGF in form of
gel
 indication: diabetic ulcers
Skin substitutes
 Integra
 Dermagraft
 Apligraf
 Cultured epidermal keratinocytes
Skin substitutes
 Integra - acellular dermis composed of
bovine collagen and glycosaminoglycan
matrix on a silicone layer
 Dermagraft - dermis replacement,
composed of cultured allogeneic
fibroblasts applied on a biodegradable
sheet
Apligraf
 Biosynthetic product composed of 2 layers
 inner dermal layer – cultured human
fibroblasts in bovine collagen type 1
 outer epidermal layer – cultured epidermal
keratinocytes
 similar to human skin
Cultured epidermal keratinocytes
 allografts or autografts
 native, cryopreserved or lyophilized
 stimulate migration and proliferation of
host keratinocytes from wound edges and
from skin adnex
Dressing change
Dressing change
Dressing change
Dressing change
Dressing change
Dressing change
Compression
 Basic treatment of venous leg ulcers
Compression
 Basic treatment of venous leg ulcers
 Compression leads to healing of 70% of
venous leg ulcers smaller than 10 cm2 in 3-
6 months
 More than 50% of patients have wrong
compression
Multilayer bandage
Multilayer bandage
Multilayer bandage
Multilayer bandage
Compressive stocking for leg
ulcers
 system of 2 stockings
Contraindication of
compression
 PAOD – ABI less than 0,5
 Acute erysipelas
 Acute eczema
 Heart failure
Compressive systems
Inteligent compression
Inteligent compression
After a week
Classification of compression
bandages
 elastic
 inelastic
 stiffness
 Classification of compression
bandages:practical aspects
 Partsch H. et al, Dermatol Surg
2008;34:600-609
Compressive bandage
 4 main features: P-LA-C-E
 Pressure
 LAyers
 Components
 Elastic properties
P - pressure
 Sub-bandage
pressure
 Measured in B1
Picopress
Compression
 mild : under 20 mm Hg
 moderate: 20-40 mm Hg
 severe: 40-60 mm Hg
 very severe: nad 60 mm Hg
Compressive garments
Circaid
Circaid
Circaid
Circaid
Circaid
Circaid
Circaid
 adequate sub-bandage pressure
 easy application by patient himself
 better compliance
 improvement of quality of life
Pain
 main factor decreasing quality of life
 venous ulcers – 60-80% pacients (20% extreme
pain)
 arterial ulcers – 83%
 diabetic ulcers – 48%
 pain results in delayed wound healing
Pain
 nociceptive – in tissue damage –
stimulation of intact afferent nerve endings
 neuropathic – damage of peripheral nerves
 psychogenic – fear of the patient
Pain intensity
 VAS = visual analogue scale
0 cm 10 cm
score ≤ 3,0 cm … mild pain
score 3,0-5,4 cm … moderate pain
score ≥ 5,5 cm … severe pain
 NRS = numerical rating scale
0 1 2 3 4 5 6 7 8 9 10
Pain at dressing change
 Very often
 For 40% of patients the worst moment of
their life
 Necessity of atraumatic dressing changes