Thieme Praxis Report · Spraul M, Apelqvist J. Publishing information Thieme Praxis Report 2013; 5...

Thieme

Praxis Report11 / 2013

Skin and Foot

▶MedicalSkinCareofPatientswithDiabeticFootSyndrome

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2 Publishing information

Spraul M, Apelqvist J. Publishing information Thieme Praxis Report 2013; 5 (11): 1–20

Thieme Praxis ReportNumber 11, Volume 5, December 2013 ISSN 1611-7891

This Thieme Praxis Report is attached to the journal of Diabetologie und Stoffwechsel.

This issue of the Thieme Praxis Report has been pro-duced with the kind support of neubourg skin care GmbH & Co. KG, Greven.

EditorProf. Dr. med. Maximilian Spraul, Rheine (Germany)E-Mail: [email protected]

Prof. Dr. med. Jan Apelqvist, Malmö (Sweden)E-Mail: [email protected]

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TitelbildProf. Rolf Daniels, Tübingen

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Editorial / Content 3

Thieme

Praxis ReportEditorial Content 11 / 2013

Spraul M, Apelqvist J. Editorial Thieme Praxis Report 2013; 5 (11): 1–20

Diabetes mellitus is associated with numerous skin disorders that are hard to treat. Dry skin typical of diabetes patients is one exception and this can be treated effec-tively with a variety of external agents. Dry skin as a consequence of neu-ropathic and neuroangiopathic-dependent dysregulations is clo se associ-ated with the development of diabetic foot syndrome. As a multifactorial occurrence, the diabetic foot syndrome represents a severe complication in long-term disease progression, and in an advanced stage, it can lead to loss of foot by amputation as an unavoidable step.

To avoid this, effective treatment and especially long-term successful pro-phylaxis against diabetic foot ulcers is of decisive importance. In addi-tion to targeted implementation of therapeutic and care measures that present a multidisciplinary challenge, success in prophylactic approaches demands motivation and cooperation from patients. Thus, for instance, daily foot care by patients themselves is an effective preventive measu-re. However, besides motivation, ease-of-use and acceptability of the skin care products play an important role for the patients. From this point of view, foam-creams have proved their worth in daily foot care routine car-ried out by patients with diabetic foot syndrome.

The present publication is based on a symposium within the framework of the 48th Annual Meeting of the European Association for the Study of Diabetes (EASD) that took place in Berlin in October 2012.

This publication is intended to raise awareness of skin problems in pa-tients with diabetes mellitus, and to delineate possibilities and limitations in the treatment of and in prophylactic measures against diabetic foot ul-cers, with special reference to the use of foam-creams as effective care op-tions. We would like to thank neubourg skin care Ltd. for supporting this project and wish you, dear readers, some brisk reading and new impulses

in your daily work.

Content

2 Publishing information

3 Editorial

4 Skin Disorders in Diabetes Mellitus – A Challenge

Prof. Ehrhardt Proksch, MD, PhD, Kiel ( Germany)

7 Prevention of Diabetic Foot Ulcer – Why is it Difficult?

Prof. Maximilian Spraul, MD, PhD, Rheine ( Germany)

9 Dry Skin and Diabetic Foot Syndrome – Foam-Creams in Daily Routine Care

Prof. Thomas Haak, MD, PhD, Mergentheim ( Germany)

12 Foam-Creams – Effective Skin Care in Patients with Diabetes Mellitus

Prof. Rolf Daniels, PhD, Tübingen ( Germany)

15 Therapy of Diabetic Foot Syndrome – What Can we Expect in the Future?

Prof. Jan Apelqvist, MD, PhD, Malmö (Sweden)

Prof. Dr. med. Maximilian Spraul, Rheine (Germany)

Prof. Dr. med. Jan Apelqvist, Malmö (Sweden)


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Spraul M, Apelqvist J. Skin and Foot – Medical Skin Care of Patients with Diabetic Foot Syndrome Thieme Praxis Report 2013; 5 (11): 1–20

Praxis Report

Skin Disorders in Diabetes Mellitus A Challenge

Prof. Ehrhardt Proksch, MD, PhDDepartment of Dermatology, University of Kiel ( Germany)

Diabetes-associated skin disorders

Necrobiosis lipoidica (Figure 1) is one of the most widely known skin disorders directly as-sociated with diabetes. It appears only in about 0.3 % of patients with diabetes mellitus, but in most cases, it is associated with diabetes mel-litus (60 %) or with abnormal glucose toler-ance (20 %) [1]. Often Necrobiosis lipoidica is apparent in a patient even before diabetes is diagnosed. Treatment of this condition is dif-ficult and consists primarily of compression and topical application of corticosteroids. In some cases, spontaneous remission has been observed (15 % of cases) [2].

Granuloma annulare (Figure 2) is also thought to be associated with diabetes mellitus, al-though it is not specific for this disease. The cause of this disorder is unknown, and in some cases, there is a spontaneous remission of this lesion. Treatment consists, among others, of ap-plication of topical corticosteroids.

Diabetic Cheiropathy (Figure 3) is a frequent dermatological disease associated with diabe-tes mellitus, characterized by a thickening of the skin resulting from alterations in the con-nective tissue structure. Mostly, the skin over-lying the hand and fingers is affected, and joint involvement may also be present. Treatment is

difficult, with topical corticosteroids being fre-quently used as a dermatological intervention.

Morphea is a specific form of sclerosis (fibrosis) of the skin of unclear origin. Treatment of this condition can be attempted with topical corti-costeroids.

Bullosis diabeticorum (Figure 4) is a disorder in which bullous lesions appear predominantly in the lower extremities; these are painless and most often heal spontaneously without scar-ring. Topical treatment to prevent superinfec-tion can be useful.

(Pseudo)acanthosis nigricans (Figure 5) is an area of flat hyperpigmentation and hyper- keratosis appearing in a variety of metabolic disorders such as diabetes mellitus. Besides the treatment of the underlying disease, dermabra-sion may be useful as a therapeutic interven-tion in some cases.

Vitiligo is characterized by sharply defined de-pigmented skin areas; its cause is unknown. It has a frequency of 1 % in the general population and 4.8 % in patients with diabetes mellitus [3].

Diabetic gangrene, mal perforans and diabetic ulcers are associated with diabetic micro angio-pathy and neuropathy. To prevent disease pro-gression, in addition to local treatment mea-sures such infection prophylaxis, off-loading therapy, and in some cases, surgical interven-tion, the underlying diabetic disease must be forcefully treated.

Dry skin (Figure 6) is a widespread phenome-non in diabetes mellitus and a reflection of the disturbed tissue trophic factors in pathologi-

Diabetes mellitus is frequently accompanied by skin disorders that are either directly associated with diabetes or appear as the consequences of diabetic complications or anti-diabetic therapeutic interventions. Treat-ment of diabetes-associated skin disorders is often quite difficult. One exception is the treatment of dry skin, for which topical substances such as foam-creams are available, that help stabilizing the epidermal barrier and that improve symptoms.


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cal glucose metabolism. About 40 % of patients with diabetes mellitus suffer from dry skin [4]. Patients with pronounced dry skin may devel-op exsiccosis eczema, which is often accompa-nied by itching.

Infections

Infectious complications of the skin are frequent in diabetes mellitus and re-flect a disturbed blood sugar balance, impaired immune defense and tissue trophic response. Table 1 gives an over-view of skin infections frequently ap-pearing in patients with diabetes mel-litus.

Therapy-associated skin disorders

Lipodystrophy can appear as a conse-quence of insulin treatment. This is a condition in which there is an atrophy of fatty tissue at the site of subcutane-ous insulin injection. Lipodystrophies occur more frequently when animal insulin is used [2], but with the avail-ability of recombinant human insulin, these have become rarer [2].

Dry skin and epidermal protective function

A healthy skin barrier is crucial for the protection of an organism from me-chanical, microbial and chemical at-tacks, from fluid loss and exsiccosis (Figure 7).

The most important components of this barrier in the stratum corneum are the corneocytes and the intercellular lipid layers (ceramides). The human stratum corneum contains 360 differ-ent ceramides, assigned to 11 different classes [5]. Impaired stratum corneum, as in diabetes mellitus (“dry skin”) or atopic dermatitis, can lead to enhanced epidermal fluid loss, reduced skin hy-dration and disturbed lipid layer com-position [6, 7].

For the effective treatment of dry skin in diabetes mellitus, a variety of ex-ternal agents is available. Besides the

physicochemical characteristics and ingre-dients (see Table 2 for an overview) of these agents, the form of their application also de-termines their efficacy in treatment of dry skin and relief of symptoms. Foam-creams are well suitable because of their specific proper-ties. They are convenient and especially useful when applying to legs and feet; ease of use is an important factor since many diabetic patients

Fig. 1 Necrobiosis lipoidica.

Fig. 2 Granuloma annulare.

Fig. 3 Diabetic Cheiro-pathy.

Fig. 4 Bullosis diabeti-corum.

Fig. 5 (Pseudo)acan-thosis nigricans.

Fig. 6 Dry skin in dia-betes mellitus.

Tab. 1 Common skin disorders in diabetes mellitus patients.

Disease Pathogen Therapy

Bacterial Infections

Impetigo • Bullous form: mostly Staphylo-coccus aureus

• Non-bullous form: Staphylococci and/or β-hemolytic A- Strepto-cocci

Local or systemic antibiotics

Furuncles Purulent infection of hair follicles by Staphylococcus aureus

• Incision• Antibiotics if needed

Erythrasma Corynebacterium minutissimum • Hygiene• Stabilization of the skin milieu• Local antimycotics (Imidazole,

Fusidic acid)

Abscesses Various pathogens • Local or systemic antibiotics• Incision

Fungal Infections

Onychomycosis Nail infection, particularly with Trichophyton or Candida

Antimycotic local therapy (e. g. Ter-binafin)


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Praxis Report

have a loss of mobility because of adipositas, age and back / joint complaints. Foam-creams are readily absorbed by the skin, can be spread easily and are not sticky.

Literature1 Yosipovitch G, Hodak E, Vardi P et al. The preva

lence of cutaneous manifestations in IDDM patients and their association with diabetes risk factors and microvascular complications. Diabetes Care 1998; 21: 506–509. Erratum in: Diabetes Care 1998; 21: 1032

2 Jecht M. Hautveränderungen bei Diabetes mellitus. Diabetologe 2009; 5: 43–56

3 Dawber RP, Bleehen SS, VallanceOwen J. Vitiligo and diabetes mellitus. Br. J Dermatol 1971; 84: 600

4 Goyal A, Raina S, Kaushal SS et al. Pattern of cutaneous manifestations in diabetes mellitus. Indian J Dermatol 2010; 55: 39–41

5 Ishikawa J, Narita H, Kondo N et al. Changes in the ceramide profile of atopic dermatitis patients. J Invest Dermatol 2010; 130: 2511–2514

6 Park HY, Kim JH, Jung M et al. A longstanding hyper glycaemic condition impairs skin barrier by accelerating skin ageing process. Exp Dermatol 2011; 20: 969–974

7 Sakai S, Endo Y, Ozawa N et al. Characteristics of the epidermis and stratum corneum of hairless mice with experimentally induced diabetes mellitus. J Invest Dermatol 2003; 120: 79–85

Conclusion and guidelines for practice

Diabetes mellitus is frequently accompanied by specific or unspecific skin disorders.▶ Dry skin is a frequently present in diabetes patients.▶ Dry skin in diabetes mellitus can be effectively treated with topical subs-

tances.▶ In view of their specific properties, foam-creams are suitable for therapy of

dry skin in patients with diabetes mellitus.

Fig. 7 Disturbed skin barrier in a patient with diabetic foot syndrome: redded dry skin with deep fissures / callus.

Tab. 2 Typical ingredients in external agents for treatment of dry skin in patients with diabetes mellitus.

Ingredients

• Emulgators • Glycerin

• Petrolatum • Essential fatty acids

• Lanolin • Fatty acids and alcohols

• Urea • Ceramides (optimal molar ratios of the key lipids is important)


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Praxis Report

Prof. Maximilian Spraul, MD, PhDInterdisciplinary Diabetic-Foot-Center Rheine (Germany)

Investigations on ulcer-free survival have frequently shown that, on the one side, there are high rates of healing, but on the other, there are also many cases of recurrence. A study of 370 patients reported that initially healing was achieved in 62 %, but after two years, foot ulcers had returned in 40 of these patients [1]. The site of ulcer also played a role in the probability of recurrence: thus, plantar ulcers had an 83 % risk of recurrence, whereas ulcers in other sites had only a 54 % risk [2].

The reason why it is difficult to avoid diabetic ulcers permanently is mainly because of the multiplicity of the underlying pathogenic processes leading to ulcer formation. Among them are diabetic neuropathy (leads primarily to painless pressure ulcers), diabetic macroan-giopathy (dry gangrene) as well as infections with danger of developing septic thrombosis (wet gangrene) (Figure 1).

Measures for the prevention of foot ulcers and their recurrence

Is education of diabetes patients suitable for preventing foot ulcers? A Cochrane review of 11 studies investigating this issue comes to the conclusion that i) the studies on this issue were not of very high quality and ii) there was no evidence of positive influence of patient education on the relevant endpoints regarding diabetic foot [3]. Another Cochrane review of 5 studies investigating complex in-terventions, different combined treatment approaches and treatment levels (patient, therapist, health system) showed that the studies were of poor quality. In some of the

studies analyzed, a positive effect of complex interventions was observed, but no clear evi-dence was available [4]. The intelligence of the patients also appeared to have no par-ticular influence on the risk of recurrence of diabetic foot ulcer [5].

So, are we to assume that the battle to treat diabetic foot ulcer is already lost? No, each case offers patient-tailored opportunities to prevent development and recurrence of foot ulcers. Even if the foot ulcers are quite severe at the initial presentation, they can be treat-ed successfully and the success maintained permanently. This, however, presupposes that the patient takes his foot problem se-riously and is reliably cooperative in imple-menting preventive measures.

Early detection and early treatment – the alpha and omega of success

Detection of diabetic foot ulcers in their early stages presents a challenge. The earlier the ulcer is detected, the less pronounced are the findings and the higher is the probability of treatment success. Thus, preventive callus de-bridement as part of medical foot care is an effective prophylactic measure against recur-rence of neuropathic ulcers [6].

Prevention of Diabetic Foot UlcerWhy is it Difficult?

The challenge in the treatment of diabetic foot syndrome and associated foot ulcers lies not only in healing existing ulcers, but above all in maintai-ning the healing achieved and in preventing recurrence. For this, effective preventive measures, reliable early detection methods and, in particular, cooperation from patients are needed. If these prerequisites are met, it is possible to prevent foot ulcers permanently, and to avoid their final conse-quence, namely amputation.


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The question arises, how foot ulcers can be identified in early stages. Often, even an ex-perienced person finds it difficult to recognize a danger situation or to classify it correctly (Figure 2). In addition, many patients are un-able to make a reliable inspection of their feet because of physical impairments. However, measuring the temperature of the sole, which can be carried out by the patients themselves quite easily, represents an effective instru-ment for prevention of recurrence, and has been shown in studies to be superior to both, standard treatment as well as daily inspec-tion of the foot [7, 8]. Despite these impres-sive data, measuring the temperature of the

sole of the foot has not yet established itself in medical practice. Possibly, such measurement should be implemented more strongly in the future, especially in patients at high risk of de-veloping ulcers.

It depends on the patient

Irrespective of the diagnostic and therapeu-tic measures implemented, the key factor in the success of therapy is the attitude and co-operation of the patient. Thus, a patient with a Charcot foot walking around in sandals is at higher risk of developing ulcer than a patient, as shown by the case report above, who active-ly participates in preventive measures.

Literature1 Pound N, Chipchase S, Treece K et al. Ulcerfree

survival following management of foot ulcers in diabetes. Diabet Med 2005; 22: 1306–1309

2 Peters EJ, Armstrong DG, Lavery LA. Risk factors for recurrent diabetic foot ulcers: site matters. Diabetes Care 2007; 30: 2077–2079

3 Dorresteijn JA, Kriegsman DM, Assendelft WJ et al. Patient education for preventing diabetic foot ulceration. Cochrane Database Syst Rev 2010; CD001488.pub3

4 Dorresteijn JA, Kriegsman DM, Valk GD. Complex interventions for preventing diabetic foot ulceration. Cochrane Database Syst Rev 2010; CD007610

5 Kloos C, Hagen F, Lindloh C et al. Cognitive function is not associated with recurrent foot ulcers in patients with diabetes and neuropathy. Diabetes Care 2009; 32: 894–896

6 Plank J, Haas W, Rakovac I et al. Evaluation of the impact of chiropodist care in the secondary prevention of foot ulcerations in diabetic subjects. Diabetes Care 2003; 26: 1691–1695

7 Lavery LA, Higgins KR, Lanctot DR et al. Preventing diabetic foot ulcer recurrence in highrisk patients: use of temperature monitoring as a selfassessment tool. Diabetes Care 2007; 30: 14–20

8 Armstrong DG, HoltzNeiderer K, Wendel C et al. Skin temperature monitoring reduces the risk for diabetic foot ulceration in highrisk patients. Am J Med 2007; 120: 1042–1046

Fig. 1 Pathogenetic varieties in diabetic foot ulcer: a) ischemic dry gangrene; b) wet gangrene in septic thrombosis; c) plantar ulcer in diabetic neuropathy; d) footwear unsuitable for ulcer prophylaxis.

Fig. 2 Diabetics foot syndrome: callus with hemorrhage as an early warning signal of the danger of ulcer development.

Conclusion and guidelines for Practice

▶ Prevention of diabetic foot ulcers is difficult, particularly in patients with “high-risk feet“ (feet with deformities).

▶ The most important factor is the attitude of the patient. Only if the patient is cooperative, measures such as appropriate shoes, foot care and educa-tion can make their contribution.

▶ Monitoring temperature in high-risk patients might be an effective tool for early detection.

▶ By preventing development of ulcers with deep infection, amputation can be avoided.

(a) (b) (c) (d)


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Diabetic autonomic polyneuropathy is one of the main factors for the development of dry skin in patients with diabetes mellitus. To-gether with other diabetes-associated disor-ders, dry skin is an important cause of diabetic foot complications such as diabetes foot ulcer (Figure 1). The dermal barrier is weakened in dry skin, facilitating the entry of pathogens and promoting epidermal injury. Dry skin is also frequently accompanied by paresthesias, pruri-tus and hypersensitivity, further increasing the vulnerability to foot complications.

The prevalence of diabetic foot ulcers is 1.7–3.3 % in patients below 50 years and 5–10 % in those above 50 years [1]. However, polyneu-ropathy and dry skin are not the only causes of ulcer development. The pathogenesis of dia-betic foot ulcer is multifactorial and besides pe-ripheral sensomotoric and autonomic neurop-athy as well as micro- and macroangio pathy, other factors such as diabetic retino pathy (foot injuries because of impaired vision), poorly controlled metabolism (accompanied not in-frequently by other metabolic disorders such as lipid metabolism or alcohol abuse), fungal infections (entry primarily via the toe nails) or unsuitable shoes also play a role. The main fac-tors, however, are nerve and vessel damage; pa-tients in whom both of these diabetes compli-cations appear at the same time are at high risk of developing ulcers [2]. Risk of recurrence of diabetic ulcers is high, with reports of a recur-rence rate of 70 % after 5 years [3]. For many pa-tients, the final consequence is an amputation of the foot or part of the foot. According to the „Inter national Working Group on the Diabetic foot”, on average every 30 seconds someone is losing his lower extremity as a consequence of diabetes. Risk of amputation depends on so-

matic as well as social factors (Table 1) [1], a further reflection of the complex pathogenesis of diabetic complications.

Preventive approaches to diabetic foot ulcer

The pathogenesis of diabetic foot ulcer is equally diverse as the opportunities to employ preventive treatment measures. On the one hand, adjustment of blood sugar metabolism as a measure to treat the cause of diabetes is important, but it is equally important to treat the typical concomitant diseases such as disorders of lipid metabolism or arterial hypertension. For instance, arterial thrombo-

Prof. Thomas Haak, MD, PhDDiabetes Center Mergentheim (Germany)

Dry Skin and Diabetic Foot SyndromeFoam-Creams in Daily Routine Care

Not infrequently patients are negligent in taking care of their diabetic foot. There is a variety of causes behind such neglect. Besides aspects of fashion such as the shape of the shoes, there are other factors that play a decisive role: ignorance of possible consequences of diabetic foot ulcers, suppression mechanisms as well as practical reasons such as sticky or slippery agents that prevent self-care of diabetic foot. Therefore, it is important that, among other factors, patients get adequate information and employ external agents that are easy and practical to use.

Tab. 1 Somatic and social risk factors in diabetic foot syndrome; modified according to [1].

Somatic Risk Factors Social Risk Factors

Poor metabolic adjustments Low social status

Prior ulcer / amputation Low educational level

Small injuries Unemployed

Biomechanical disturbances Living alone or divorced

Neuropathy and / or angiopathy Poor access to healthcare services


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Praxis Report

ses can be prevented by platelet aggregation inhibition with acetyl salicylic acid (ASS). Be-yond that, improvements in life style such as physical activity, normalization of weight or nicotine abstinence can reduce the risk of ul-cers. Finally, daily care of the diabetic foot by the patient himself is important for the long-lasting success of preventive measures. This can be achieved by the use of appropriate and easy-to-use skin care products.

How to raise awareness in diabetes patients to the dangers of diabetic foot?

A frequently encountered problem in the pre-vention of diabetic foot ulcers is patients’ lack of awareness of the problem. One’s foot is often the scene of secondary importance compared to other “larger” problems such as the threat of

blindness or existentially threatening concomi-tant diseases such as a stroke or heart attacks; foot problems get pushed into the background as well when facing social challenges such as unemployment, marital problems or social isolation. In addition, foot ulcers represent a lifelong threat, and this awareness can be easily suppressed during acute problem-free phases according to the motto “out of sight, out of mind”. Furthermore, fashion considerations can prevent patients from wearing “diabetes shoes”, leading to a preference for shoes that are possibly too small. Diabetes patients also underestimate the danger of minor wounds and small lesions which can be hidden in shoes even in advanced stages. In diabetic neuro-pathy, even massive foot problems can cause little or no pain, so that for the patients, the level of suffering remains rather low over a long period of time.

An effective measure to prevent foot ulcers in the treatment of diabetes patients is, therefore, a foot-specific educational program such as the “German Barefoot Program”. This programme teaches the importance of healthy and well-functioning feet, explains the damage to foot that neuropathy and angiopathy can cause and the expected consequences of this damage. The patient must be taught how to carry out ef-fective foot care, and what he has to do in an emergency situation. Treatment of dry skin, a key element in preventing foot ulcers, is of-ten neglected by patients. “I forgot it totally”, “Creams make my feet very slippery, and I don’t want to have a fall”, or, “Creams make my socks and shoes dirty”. These are typical statements

Fig. 1 Dry skin and diabetic foot ulcer on the lateral edge (left leg) in a patient with diabetes mellitus type 2.

Fig. 2 Foam-cream containing 10 % urea compared to baseline: a) significantly higher levels of plantar skin moisturization by use of foam-cream compared to baseline b) significantly more frequent regression in the clinical picture of dry skin with use of a foam-cream compared to baseline.

10

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made by patients when asked concrete ques-tions about their use of foot care products.

Acceptance of foam-creams in daily use was investigated in a total of 92 diabetes patients regarding the aspect of ease-of-use. Compared to baseline values, after four weeks, plantar skin was found to be moisturized to a signifi-cantly higher degree and there was also found a significantly more frequent regression of the clinical picture of dry skin when a foam- cream with 10 % urea was used (Figure 2).

Patients expressed high levels of personal satis-faction; 85 % confirmed that the foam-cream was absorbed by the skin rapidly and complete-ly, and 82.5 % reported that they could put on their socks without any problem immediately after applying the foam-cream. These results are in agreement with those of previous stud-ies (e. g. [4]).

Literature1 Morbach S, Müller E, Reike H et al. Diagnostik, The

rapie, Verlaufskontrolle und Prävention des diabetischen Fußsyndroms. Evidenzbasierte Leitlinie der Deutschen DiabetesGesellschaft, Update 2008

2 Kumar S, Ashe HA, Parnell LN et al. The prevalence of foot ulceration and its correlates in type 2 diabetic patients: a populationbased study. Diabet Med 1994; 11: 480–484

3 Apelqvist J, Larsson J, Agardh CD. Longterm prognosis for diabetic patients with foot ulcers. J Intern Med 1993; 233: 485–491

4 Proksch E. Wirksamkeitsprüfung und Anwendungstest mit „Allpremed diabetic 10 % Urea Fuß plus“. Universitätsklinikum SchleswigHolstein 2006

Conclusion and guidelines for practice

Diabetic foot ulcers represent a grave danger to diabetes patients with diabe-tic neuropathy and/or angiopathy.▶ Patient‘s understanding of the need for individual skin care for prevention

of foot ulcers is the precondition for successful reduction of amputation frequency.

▶ Foam-creams are effective external agents in the treatment of dry skin and are also well-accepted by patients.


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Healthy skin is an effective barrier and pro-tects the organism from a variety of external influences such as mechanical stress, fluctua-tions in temperature and microbial attacks.

Such protection is offered primarily by the epidermis which is among others composed

of corneocytes and an extracellular lipid ma-trix [1].

In patients with diabetes mellitus, the lipid matrix is altered, leading to deterioration of the epidermal protective function. Clinically this manifests, for instance, as dry skin, scaling and pruritus. Besides the reduction of com-plaints, effective skin care of diabetic patients should, therefore, aim for supplying of mois-ture and lipids to the skin and the restoration of the epidermal protective function.

To achieve this, a number of skin care prod-ucts are available such as water-oil, oil-water or mixed emulsions, gels and foam-creams [2].

Prof. Rolf Daniels, PhDPharmaceutical Technology, University of Tübingen (Germany)

Foam-CreamsEffective Skin Care in Patients with Diabetes Mellitus

The protective function of the epidermis in patients with diabetes mellitus is often impaired; dry skin is the result of impaired epidermal lipid layers and increased transepidermal water loss. In these patients, effective skin care should guarantee the regulation of skin hydration and supply of lipids, without occluding the skin surface. With their specific properties, foam-creams meet these demands and have proved their therapeutic success in patients with diabetes mellitus and dry skin.

Fig. 1 Dry skin care. Above: Occluding skin care without positive long-term effect. Below: ideal skin care with increasing hydration and decreasing transepidermal water loss.

(a)

(b)

TEW

LH

ydra

tion

day 1

TEWL = transepidermal water loss

day 14day 8

occluding skin care

TEW

LH

ydra

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day 1

TEWL = transepidermal water loss

day 14day 8

”ideal“ skin care


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While choosing a product for treating dry skin in patients with diabetes mellitus, its effect on the epidermis and the epidermal water and lipid status should be considered. Thus, use of hydrophilic oil-water emulsifiers washes out lipids of the stratum corneum, and as a con-sequence, the epidermal barrier is damaged, leading to increased transepidermal water loss.

Other products with a high fat content can re-sult in complete occlusion of the skin surface, leading to hyperhydration of the epidermal lipid matrix. If the occluding layer is removed, it leads to an increased transepidermal water loss, and reactively to an increased dehydration of the skin.

What then are the demands placed on an “ ideal” skin care product in diabetes patients? Unlike occluding products that after applica-tion initially cause hyperhydration and there-after lead to increased trans epidermal wa-ter loss and decreased hydration, an “ideal” skin care product would lead to a gradually increasing hydration over a period of time and a decrease in transepidermal water loss ( Figure 1).

Foam-creams in the treatment of dry skin in diabetes patients

Foam is a dispersion of gas in liquid and is as-sociated in daily life mostly with positive feel-ings (milk froth on a cup of tasty cappuccino, a foaming warm bath, a piece of fresh fruit cake with whipped cream). Foam-creams also im-part a positive feeling by virtue of their pleas-ant look and feel.

Most of the commercially available foam-creams are aerosol foams, with the emulsion in the spray can being foamed up with a pro-pellant gas. Different propellant gases are used (Table 1), most frequently butane, propane and mixtures of these two.

Foam-creams have a number of advantages over skin care creams out of tubes or jars.

Spray cans under pressure dispense foam-cream in a very clean and hygienic way (something that is especially advantageous in cases of infected skin), allow small dos-ages, and the product is protected from contamination. Also, normally, very small amounts of preservatives are needed, and sensitive ingredients are protected by the airtight and opaque packaging (mostly alu-minum).

The content of the spray can usually has a wa-ter phase and an oil phase, suitable emulga-tors and a propellant. The composition of a foam-cream is thus not significantly different from that of other skin care products, except for the addition of propellant gases and the lack of preservatives (Table 2). Foam develops at the moment when the emulsion is ejected out of the nozzle of the aerosol can.

Tab. 1 Propellant gases suitable for foaming of creams.

Liquid gas Compressed gas

N2O CO2

Propane, Butane and Isobutane

N2

Dimethyl ether

HFAs (Hydrofluoralkanes)

Tab. 2 Foam-cream ingredients (Allpresan® Diabetic Intensive).

Ingredients

Water Stearic acid Allantoin

Urea Propylene glycol Potassium lauroyl wheat amino acids

Butane Glycerin Palm glycerides

Decyl oleate Glyceryl stearate Capryloyl glycine

Octyl dodecanol Panthenol Sodium lauroyl sarcosinate

Cetearyl alcohol Saccharide isomerate Sodium citrate

Propane Undecyl alcohol Citric acid

Fig. 2 Creams enriched with fluorescent dye. Left: customarily used cream, uneven spreading; right: foam-cream, evenly spreaded.


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Praxis Report

Properties of Foam-Creams

A typical characteristic of foam-creams is the “relative foam density” determined by measur-ing the volume increase during the foaming process. In foam-creams there is a 10-fold in-crease of volume.

Thus, foam-creams have special characteristics. Often, the usually used creams are spreaded unevenly when applied, whereas foam-creams can be spreaded very evenly, reaching even into the space between toes and fingers (Figure 2).

The water content of the foam-cream prepa-rations also evaporates more rapidly from the skin surface than that of the usual creams (Figure 3).

On the one hand, this implies a better cool-ing effect for the patient, and on the other, the product converts faster into a lipophilic form, resulting in a higher concentration of the effective substances (e.g. urea) and better absorption through the skin.

However, a foam-cream does not lose its foam character even during the drying process. Even after 30 minutes, when the water con-tent of the foam-cream is lost to a great ex-tent by evaporation, individual foam bubbles can be seen under the microscope (Figure 4). This implies, that no occluding cream layer is formed and transepidermal water exchange between epidermis and the external world is maintained.

Besides the positive characteristics of foam-creams which have been proven in the treat-ment of dry skin in patients with diabetes mellitus, they can be used very sparingly in comparison with the customary products and are thus economical in use.

Literature1 Proksch E, Brandner JM, Jensen JM. The skin: an in

dispensable barrier. Exp Dermatol 2008; 17: 1063–1072

2 Dermokosmetika zur Reinigung und Pflege trockener Haut. Leitlinie der GD Gesellschaft für Dermopharmazie e. V. 2009

Fig. 3 Speed of evaporation after application of cream products: after foam-cream application, contained liquid evaporates from the skin surface more rapidly than that of other creams (emulsion).

Fig. 4 Foam-cream during evaporation: foam structure is maintained without occluding cream layer.


▶ The use of foam-creams in the treatment of dry skin is in accordance with the guidelines of the Society for Dermopharmacy.

▶ Foam-creams distinctly differ from custo-mary products in the properties of their substances.

▶ Diabetes patients profit by using foam-creams - these products are hygienic and easy-to-use, can be applied easily even over difficult-to-reach sites, are rapidly absorbed by the skin, are effective, do not occlude the skin surface and are economically in use.

20

40

60

80

100

0

0 10 20 30

Resi

dual

moi

stur

e (%

)

■ Foam-cream ■ Emulsion

Time (min)


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Praxis Report

The development of diabetic foot ulcer is a complex occurrence; disturbed glucose me-tabolism leads to neuropathic and (neuro)angiopathic-dependent dysfunctions of tissue and structure of the diabetic foot (Table 1). Over a period of time, the architecture of the entire foot can suffer massive damage, devel-oping a vicious circle of neuropathic paresthe-sias, foot deformities, functional impairment and ulcer formation which is quite difficult to break.

Mechanical stress, shear forces

In most cases, among other factors, pathologi-cally elevated pressure with unnoticed load peaks on individual areas of the foot, especial-ly in the forefoot, plays an important role in ulcer formation. It has been shown that pres-sure-relieving measures can effectively reduce these loading peaks. Thus, use of Total Contact Casts (TCC) led to a 87 % reduction of loading peak, removal of calli led to a 30 % reduction and other measures such as wearing diabetes shoes also considerably reduced the loading peak (16–52 %). If the pressure on the affected area was reduced below 200 kPa (previously up to 600 kPa), a recurrence in this region was unlikley [1].

Infections

Infections represent a grave danger to the diabetic foot. Since the affected extremity is exposed to existential danger, each infected diabetic foot ulcer must receive a maximum of diagnostic and therapeutic attention. Fur-thermore, infections of diabetic foot ulcers are

frequently polymicrobial [2]. Risk of infection of an ulcer increases with depth of wounds to the bone, in cases with long-standing wounds (> 30 days), in recurrent lesions, in traumatic injuries and in patients with peripheral angi-opathy [3]. It is absolutely important to pay attention to the infected tissue. An overview of the recommendations of the „International Working Group on the Diabetic Foot” on an-tibiotic treatment procedures in diabetic foot ulcers is given in Table 2.

Peripheral Macroangiopathy

For the development as well as for healing of foot ulcers, circulation in the relevant ex-tremity is a key factor. Whereas for a long time, blood vessels to the foot were in the fo-cus of therapeutic measures, more attention is being paid to the blood vessels within the foot now. With the increasing use of endo-vascular techniques, more distal vessels can be reached and successfully reconstructed. The timing is of crucial importance: thus, a neuro ischemic foot ulcer in an advanced stage might reflect a multiorgan disease with an altogether poor prognosis. Also, infections and extensive tissue involvement reduce the

Prof. Jan Apelqvist, MD, PhDDiabetîc-Foot-Center, University Clinic Skåne, Malmö (Sweden)

Therapy of Diabetic Foot SyndromeWhat Can we Expect in the Future?

Diabetic foot ulcer, with its multifactorial pathogenesis, and the large variety of treatment approaches available, represents a great challenge to patients, therapists and the entire healthcare system. For a long time, diabetic neuropathy was at the foreground of considerations in diabetic foot syndrome; now, there is once again a strongly therapeutic focus upon ischemic and neuroangiopathic components of the disease. Not least, the challenge is to treat infections in a systematic and targeted manner. It remains to be seen which novel treatment approaches will prevail in the future.


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Praxis Report

prospects of successful healing. This implies that revascularization must be carried out in a timely fashion for achieving positive effects for the patient – attention needs to be paid to all the concomitant health conditions such as kidney and cardiac insufficiency or cardio-vascular end organ damage, as well as to oth-er factors such as life expectancy, mobility and walking distance. Revascularization must be part of a multimodal procedure compris-ing not only the restoration of circulation, but also appropriate medical treatment of any in-flammation present, and the possible use of hyperbaric oxygen (HBO).

Additional Therapy Approaches

The aim of treatment in diabetic foot syn-drome is to restore its usability: to enable a patient to maintain ambulation and walking capacity. In order to speed-up wound heal-ing, it is meaningful to treat the wound with negative pressure (V.A.C. = Vacuum Assisted Closure). Established with a vacuum pump, V.A.C. is leading to accelerated granulation formation and wound retraction, disappear-ance of wound edema, lowering of infection rate and shortening of time to wound closure (Figure 1) [4]. Since V.A.C treatment requires high technical outlay and should be carried out only by trained personnel, application is only useful in selected cases.

Hyperbaric oxygen therapy (HBO = hyperbar-ic oxygen) might also contribute to accelera-tion of wound healing in diabetic foot ulcers. Thus, after a treatment period of 12 months, the healing rate of diabetic foot ulcers under HBO was 61 % as against 27 % under placebo treatment (p = 0.009) [5]. HBO is employed primarily in patients with a long history of the disease and an unsatisfactory healing tendency; transcutaneous PO2 measurement (TcPO2) is a possible predictor of therapy suc-cess.

Debridement has long been a primary com-ponent of wound treatment in diabetic foot syndrome. Today, a series of techniques are available for wound debridement that en-ables a targeted removal of necrotic tissue

Tab. 1 Diabetic foot ulcer – a complex occurrence: Dysfunctions of the diabetic foot.

Dysfunctions

Disturbances of skin sensations

Muscle atrophy/weakness

Limited joint mobility

„Stiff foot“ syndrome

Disturbed foot dynamics/biomechanics

Disturbed proprioception

Foot deformities

Arteriovenous shunts

Osteoarthropathy

Changes in gait

Sweating – dry skin – callus formation

Atrophy of subcutaneous fat pads

Ischemia in peripheral arterial occlusive disease

Tab. 2 Antibiotic approach to diabetic foot ulcers (Recommendations of the “International Working Group on the Diabetic Foot“ 2011 [12].

Antibiotic approach

Clinically non-infected skin injuries need no antibacterial treatment.

Swabs from deeper wound areas enable more reliable pathogen identification than surface swabs (contamination).

Pathogen identification from bone samples in osteomyelitis increases the success rate of antibiotic therapy.

Available data do not permit statements on the advantages of any specific antibiotic therapy strategy (class of substance, application method, therapy duration).

Initially, antibiotic therapy should be empirical including therapy against Staphylo-coccus aureus und aerobic Streptococci.

Antibiotics against gram-negative pathogens are indicated in the treatment of pa-tients with severe infections or in areas with high prevalence.

If an adequate antibiogram is available, therapy change to a specific antibiotic drug can be considered; however, clinical response to empirical therapy must be conside-red.

Severe infections require intravenous therapy; less severe infections can be treated with oral antibiotics with higher bioavailability.

Tab. 3 Debridement techniques in the treatment of diabetic foot syndrome.

Debridement techniques

Surgical

Mechanical (moist to dry)

Chemical (for example hypochloride)

Enzymatic

Hydrotherapy and rinsing

High pressure therapy

Autolytic preparations (foam-creams, films, hydro-gels, hydrocolloids)

Osmotic preparations

Maggot therapy

Negative pressure therapy


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Praxis Report

without endangering healthy tissue to any great extent (Table 3).

Multidisciplinary Treatment

Diabetic foot syndrome is an expression of a complex systemic disease. Comparative stud-ies have shown that multidisciplinary ap-proaches in treatment resulted in improved rates of healing and a reduction in the fre-quency of amputations [6–11].

Literatur1 Cavanagh PR, Bus SA. Off-loading the diabetic foot

for ulcer prevention and healing. J Vasc Surg 2010; 52: 37S–43S

2 Vardakas KZ, Horianopoulou M, Falagas ME. Factors associated with treatment failure in patients with diabetic foot infections: An analysis of data from randomized controlled trials. Diabetes Res Clin Pract 2008; 80: 344–351

3 Lavery LA, Armstrong DG, Wunderlich RP et al. Risk factors for foot infections in individuals with diabetes. Diabetes Care 2006; 29: 1288–1293

4 Blume PA, Walters J, Payne W et al. Comparison of negative pressure wound therapy using vacuumassisted closure with advanced moist wound therapy in the treatment of diabetic foot ulcers: a multicenter randomized controlled trial. Diabetes Care 2008; 31: 631–636

5 Löndahl M, Katzman P, Nilsson A et al. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care 2010; 33: 998–1003

6 McCabe CJ, Stevenson RC, Dolan AM. Evaluation of a diabetic foot screening and protection programme. Diabet Med 1998; 15: 80–84

7 Dargis V, Pantelejeva O, Jonushaite A et al. Benefits of a multidisciplinary approach in the management of recurrent diabetic foot ulceration in Lithuania: a prospective study. Diabetes Care 1999; 22: 1428–1431

8 Krishnan S, Nash F, Baker N et al. Reduction in diabetic amputations over 11 years in a defined U.K. population: benefits of multidisciplinary team work and continuous prospective audit. Diabetes Care 2008; 31: 99–101

9 Zayed H, Halawa M, Maillardet L et al. Improving limb salvage rate in diabetic patients with critical leg ischaemia using a multidisciplinary approach. Int J Clin Pract 2009; 63: 855–858

10 Apelqvist J, Larsson J. What is the most effective way to reduce incidence of amputation in the diabetic foot? Diabetes Metab Res Rev 2000; 16: S75–S83

11 Aydin K, Isildak M, Karakaya J et al. Change in amputation predictors in diabetic foot disease: effect of multidisciplinary approach. Endocrine 2010; 38: 87–92

12 International Working Group on the Diabetic Foot. International consensus on the diabetic foot and practical guidelines on the management and the prevention of the diabetic foot. Amsterdam, the Netherlands (2011). Available on CDROM at www.idf.org/bookshop or (www.diabeticfoot.nl)


▶ Diabetic foot ulcer is a complex occurrence and is associated with dysfunc-tions and deformities of the diabetic foot.

▶ Besides diabetic neuropathy, peripheral arterial occlusive diseases and infections are important factors for the development and outcome of dia-betic foot ulcers.

▶ Only a structured treatment which takes into account all aspects of diabe-tic foot ulcers enables long-lasting success. This represents a multidiscipli-nary challenge.

Fig. 1 Standard treatment to achieve moist wound healing vs. negative pres-sure treatment (V.A.C. = Vacuum-Assisted Closure): significantly faster wound closure under V.A.C. (p = 0.001) [4].

20

40

60

80

100

0

0 50 100 150

Patie

nts

(%)

■ Negative pressure treatment (V.A.C.)■ Moist wound healing

Time to wound healing (days)


Increase in skin moisture as a %70

35

07 days 28 days

+ 62.6+ 50.9

Source: Wigger-Alberti W. et al. Clinical Investigation Reportbioskin GmbH, June 2011, duration = 28 days, n = 20, data on file.The clinical study revealed an increase of 62.6% in the skin moisture of diabetics.

Skincare for diabeticsWhat do foam creams achieve?

The skin’s natural functions are maintained

Foam cream

Skin

Protection

The patented innovative active technology forms a cellular, two-dimensional protective mesh.

After After After After After

Start 1 hr 2 hrs 4 hrs 6 hrs 8 hrs

24 ±4 22 ±6 25 ±6 19 ±4 23 ±6 24 ±6

23 ±6 26 ±5 34 ±6 39 ±4 38 ±6 37 ±8

Allpresan® diabetic foam cream with the patented, actively breathable formula.

Relative moisture level

Day 2(pretreated)

Day 1(not pretreated)

PD Dr. Reimar Rudolph , Norden

Comparison of the moisture values with and without application in the morning of a foam cream containing 10% urea on 33 patients with insu-lin-dependent dia-betes and early-stage diabetic foot syndrome over 8 hours.

Effective protection and repair

Allpresan® diabetic foam creamwith the patented,

actively breathable formula.Can be used even between the toes.

Allpresan® – for medical skincare.

GERM

AN TECHNOLOGY

GERMAN TECHNOLOGY

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