Lymphoedema and chronic wounds

Lymphoedema is a chronic inflammatory disease of the interstitium as a result of primary (congenital) or secondary (acquired) damage to the lymphatic drainage system, which is characterized by inflammation, increased fat deposits and tissue fibrosis. Despite earlier hypotheses that considered lymphoedema to be a disease solely due to a mechanical disorder of the lymphatic system, the progressive inflammation underlying this disease is now well established, so that further treatment options need to be considered in the future.

Lymphoedema is a chronic inflammatory disease of the interstitium resulting from primary (congenital) or secondary (acquired) damage to the lymphatic drainage system [1], which is characterized by inflammation, increased fat deposits and tissue fibrosis [2,3]. Despite earlier hypotheses that considered lymphoedema to be a disease solely due to a mechanical disorder of the lymphatic system, the progressive inflammation underlying this disease is now well established [3], so that further treatment options need to be considered in the future.

Edema (from the ancient Greek οἴδημα oídēma, meaning “swelling” or “dropsy”) is a swelling of body tissue due to an accumulation of fluid from the vascular system. If the balance between filtration on the one hand and lymph drainage on the other is shifted in favor of filtration, then more fluid remains in the tissue. The result is an accumulation of water in the extravascular intercellular space, i.e. edema.

All peripheral edema is due to an accumulation of fluid in the interstitium. If capillary filtration increases, e.g. due to venous hypertension, lymphatic drainage increases until it has reached its maximum transport capacity and the remaining fluid remains in the tissue; there is no reabsorption into the veins in homeostasis [4,5].

Lymphoedema can be defined as tissue swelling caused by a disorder of the lymphatic system (LGS). In clinical practice, however, chronic swelling can be due to a number of causes such as venous disease, immobility, chronic heart failure, obesity and medication.

To cover this broad spectrum of causes, the term “chronic edema” was coined to create a standardized definition for use in prevalence studies. It should be noted: All edema is caused by an insufficiency of the LGS, but not all edema is lymphedema.

Forms of insufficiency [6] (Table 1).

High volume or dynamic insufficiency

There is a water overload with normal function of the lymph vessels, e.g. in the case of inactive edema, CVI stage 1 (C3, CEAP classification), hypoproteinemia and premenstrual syndrome. We speak of a dynamic or high-volume insufficiency, the transport capacity of the lymph vessels (TC) is normal, the lymphatic time volume (LTV) is at the upper limit of the norm, the lymphatic load (LL) is higher than the TC. Treatment consists of compression to reduce LL in CVI and inactivity edema.

Mechanical insufficiency

The lymphatic system is damaged and lymphoedema develops as a result. Lymphoedema means primary or secondary damage to the LGS, the TC is lower than normal, the LZV is reduced, the LL is within the normal range. The treatment consists of 2-phase therapy for lymphoedema.

Safety valve insufficiency or combined insufficiency

The TK and LZV are initially normal, but as the LL increases, the TK and LZV begin to decrease, e.g. in acute inflammation, in which the tissue hormones dilate the lymph vessels, or in right heart failure, in which the lymph drainage to the right heart is blocked and thus the inflow of lymph to the heart is prevented. Reflux occurs. The 2-phase therapy of lymphoedema is also used for this form of insufficiency, as the transport capacity in the affected area is reduced.

Wounds – an inflammation in the tissue

Inflammation is the body’s reaction to cell destruction caused by various factors: Bacteria, viruses, fungi, parasites, chemicals, heat, cold and autoimmune diseases.

With the knowledge of molecular biology, which was not available before the 1960s, it is possible to define inflammation in a broader sense as a protective response involving the activation of immune and non-immune cells in response to a damaged cell, with the aim of restoring tissue homeostasis [7].

Inflammation is the first phase of the wound healing process. This is normally followed by two further phases: Regeneration (sometimes referred to as proliferation) and maturation. Inflammation is characterized by the classic signs such as heat, redness, swelling, pain and restricted movement. The general function of inflammation is to neutralize and destroy toxic substances at the site of injury and to restore tissue homeostasis [8].

Chronic wounds

Non-healing chronic wounds represent a major biological, psychological, social and financial burden both for the individual patient and for the healthcare system in general. Pathologically extensive inflammation plays an important role in interrupting the normal healing cascade. The causes of chronic wounds (venous, arterial, pressure and diabetic ulcers, etc.) can be investigated by contrasting normal healing with the abnormal inflammatory response caused by the common components of chronic wounds (aging, hypoxia, ischemia-reperfusion injury and bacterial colonization) (Fig. 1). Care of the wound bed through debridement, dressings and antibiotics currently forms the basis of treatment [9].

A chronic wound is a wound that does not heal in an orderly fashion and within a predictable period of time, or wounds that do not heal within three months. Chronic wounds often remain in the inflammatory stage for too long and may never heal or may take years to heal. Patients with chronic wounds often report that pain dominates their lives. They are the main problem for patients with chronic ulcers.

Ulcer cruris

The venous and lymphatic systems are “inseparable” dual drainage systems. Although they operate according to two completely different, independent principles of fluid dynamics and the critical differences in rheological properties between the venous (weakly fluctuating flow) and lymphatic (peristaltic flow) systems are maintained, they retain a “complementary” function. In this context, inflammatory processes by leukocytes and macrophages affect the venous endothelium and promote a complex sequence of events in which adhesion molecules, chemokines, cytokines, growth factors and proteases are activated, causing endothelial dysfunction and dysregulation, compromising tissue integrity and ultimately leading to skin damage and ulceration.

Therefore, the failure of one system leads to an additional load on the other system. If this overload exceeds the maximum capacity of the compensation function of the other system, this leads to the failure of both systems together.

Long-term failure of one system leads to “total” failure of this interdependent dual system, resulting in a new condition known as “phlebolymphedema” (PLE), a combined condition of chronic venous and chronic lymphatic insufficiency (CVI, CLI) [10].

A leg ulcer is a wound on the leg that does not heal. The most common cause of an open leg is chronic venous disease (around 70 percent). This can essentially be caused by the following factors: varicose veins (varicosis), post-thrombotic syndrome (valve destruction and vein wall changes after deep vein thrombosis), failure of the venous pumping function (with reduced mobility in the ankle joint), pinching of the venous return flow in the groin regions with extreme obesity (dependency syndrome). Rarer causes are vascular inflammation, infections, nerve conduction disorders, drug side effects, malignant skin diseases, autoimmune diseases and other rare diseases.

According to the “Bonn Vein Study” from 2003, the prevalence of leg ulcers in Germany is 0.2-0.3%. This is strongly dependent on age and rises to 2.5% in the 70+ age group [11].

The basic therapy for PLÖ consists of 2-phase therapy as for lymphoedema, whereby compression therapy is the mainstay of therapy, regardless of the aetiology of the disease. Compression therapy is based on CDT (complex decongestive therapy) to control CVI and CLI(10) at the same time (Fig. 2).

Compression therapy

Evidence of mechanical compression therapy for injuries was found as early as the Neolithic period in the drawings of the Tassili caves in the Sahara and in the Edwin Smith Papyrus.

Compression therapy is an indispensable part of the decongestion and maintenance phase. Their effects:

• Normalization of pathologically increased ultrafiltration with consecutive reduction of the lymphatic load
• Increased inflow of interstitial fluid into the initial lymph vessels
• Displacement of the fluid through the tissue gaps
• Increasing the lymph flow in the still functioning lymph vessels
• Reduction of venous pressure and thus an anti-oedematous effect
• Improvement of tissue findings in phase II [12,13].

Compression therapy is the basic treatment method for venous leg ulcers, which has proven to be effective for healing and also for maintaining them. In each individual case, the underlying venous pathology must be identified, preferably by duplex examination, and methods to correct the pathophysiology by surgery or sclerotherapy must be considered. Various aids can be used for the compression therapy of venous ulcers. Medical compression stockings are considered for the treatment of venous ulcers if the ulcers are not too large and have not been present for too long. In the routine treatment of venous ulcers, stockings cannot replace compression bandages, as these can exert a much higher pressure. Elastic, elongated material is relatively easy to handle and can also be used by patients. In contrast to the inelastic material, these bandages generate an active force through the elastic constriction of their fibers. Inelastic material produces a significantly higher rise than elastic material when standing up and during dorsiflexion. Single-layer bandages are applied with an overlap of approximately 50%. Single-layer dressings are not sufficient to treat a venous ulcer. A multilayer bandage can consist of one or more components of different compression materials [14].

Treatment with compression therapy leads to healing, which is associated with a reduction in proinflammatory cytokines and an increase in the anti-inflammatory cytokine IL-1-Ra [15].

Compression therapy: The intensity of the lymphological compression bandages must be varied, both in terms of the compressive pressure and the padding materials [16].

The lymphological compression bandage (LKV) (Fig. 3 ) can be designed as an alternating or permanent bandage. A new dressing is applied daily and ideally left in place overnight. In contrast, the permanent dressing, e.g. with multi-component systems, remains in place for a longer period of time, usually several days, even overnight [17].

Unfortunately, in practice we find that it is not easy to stabilize the volume during the maintenance phase. This is confirmed by scientific studies on patients with lymphoedema of the lower limbs [18]. Furthermore, not only the patient but also experienced medical staff – doctors, physiotherapists, nurses – are often unable to apply the correct compression pressure when self-bandaging [19].

How should the patient achieve the correct pressure under the LKV?

A firm, rigid bandage with Velcro fasteners that can be readjusted when the oedema is reduced (Medical Adaptive Compression Systems, MAK) was then developed ( Figs. 4 and 5 ). MAKs are also known as Velcro or wrap bandages. When installed, the systems have a high level of strength. They can consist of calf, thigh and foot components as well as arm and hand components. MAK can be applied independently by the patient if they are still sufficiently mobile, but the Velcro system also makes it easier for therapists, relatives or nursing staff to apply the device [17].

In contrast to bandaging with bandages, readjusting the Velcro fasteners prevents pressure loss, which effectively promotes edema regression. Due to the significantly simpler application, such systems are less time-consuming and less error-prone in comparison to complex compression bandaging [19].

MAK achieved a significantly greater volume reduction after 24 hours than inelastic multilayer bandages (UMB). The patients were able to put on and adjust the system themselves after instruction and an initial 2-hour wearing time. Autonomous management of MAK appeared to improve clinical outcome and is a promising step towards self-management with effective compression [20].

Re-adjustable MACs with a resting pressure of around 40 mmHg are more effective in reducing chronic venous edema than UMB with a resting pressure of around 60 mmHg. MAKs are not only effective and well tolerated in maintenance therapy, but also in the initial decongestive treatment phase of patients with venous leg edema [21,22].

Compression therapy is widely recognized as the cornerstone for healing CVI and ulcers [23]. Macciò clearly shows that the inflammation of the skin of the lower leg lymphoedema has completely disappeared under the bandage, while it is still visible in the proximal parts of the limb without the bandage [24].

Based on the available literature, it can be concluded that compression, including intermittent compression, is effective in the treatment of various vascular and oedema disorders, wound healing (especially leg ulcers) [25], thrombosis prophylaxis and also in the treatment of PAD when correctly indicated.

Compression therapy therefore has a triple effect:

1. counteracts the formation of edema,
2. accelerates fluid absorption and transport in the lymphatic system and
3. reduces the edema [26].

Phlebolymphedema should be treated with all the possibilities of the CDT routine. To reduce the edema, we need compression with rigid material (high stiffness) [27,28].

There are problems with pressure in the initial phase of decongestion (studies in Germany and the UK have shown these problems) [19]Since the compression therapy reduces the accompanying edema and the bandage therefore begins to slip within a few hours of movement, the bandage would have to be renewed or corrected after approx. 5 hours; with the MAK, the Velcro fastener is only tightened. Compression stockings are worn during the maintenance phase, although there are always problems with putting on the stockings, resulting in non-compliance and recurrent ulcers. It has been proven that Velcro bandages are possible in both phases [20].

Velcro fasteners are better than inelastic bandages [22]. Self-management by the patient using the MAK is significantly improved; in addition, the required pressure can be measured and readjusted for some supports using a control card.

If the patient treats themselves with bandages, these must be removed and reapplied, whereby no statement can be made about the compression pressure. There is less variability with the MAK than with the UMB.

Conclusion

In summary, it can be said that an adjustable compression Velcro bandage as part of CDT can significantly reduce the volume similar to conventional multi-layer bandages and improve the quality of life. It is a comfortable alternative to conventional multi-layer bandages in the active treatment phase of CDT [29].

The ulcers heal significantly faster under compression than with wound dressings alone (Fig. 6A+B). Compression is the most important therapeutic pillar in the treatment of lymphoedema, venous and inflammatory oedema and chronic wounds.

Take-Home-Messages

• Extracellular edema is caused by lymph vessel insufficiency.
• The capillary filtration rate exceeds the transport capacity of the lymphatic vessels. In equilibrium, there is no resorption into the veins.
• Pro-inflammatory cytokines are secreted during inflammation.
• Chronic wounds are caused and maintained by persistent inflammation.
• In addition to wound cleansing, compression therapy is the mainstay of treatment. This reduces the pro-inflammatory cytokines and increases the anti-inflammatory cytokines.

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HAUSARZT PRAXIS 2024; 19(9): 6–11