Wound healing of chronic leg ulcers under the influence of erysipelas

ARTICLE

Auteur(s) : Dietrich TREBING, Hans-Dieter GÖRING

Municipal Hospital Dessau, Department of Dermatology and Immunology, Auenweg 38, 06847 Dessau, Germany

Article accepted 03/11/2003

In the past we have repeatedly observed that additional erysipelas can stimulate the granulation and epithelialization of, and in some cases even completely heal, chronic leg ulcers. These changes suggest a positive effect of the erysipelas to the healing of the ulcers. To our knowledge, this phenomenon has not thus far been described in the literature.

Clinical observations

We report four patients with therapy-resistant ulcus cruris, already existing for many years (2 ulcera cruris venosa [deep venous insufficiency/postthrombotic syndrome], 2 ulcera cruris mixta [superficial venous insufficiency and atherosclerotic occlusive disease]), on which a new erysipelas was superimposed. The ulcera have been treated over the years with various antimicrobial topicals, granulation supporting and fluid absorbing colloidal wound layers, compression bandages and elevation of the lower extremity without any noticeable improvement of the ulcera. Surgical interventions were either not possible or the patients did not consent. Repeated studies of serum cytokine concentration (IL-6, IL-2-receptor) were carried out. The area of the ulcera was determined planimetrically at the beginning and at the time of complete healing of the erysipelas. Treatment of the erysipelas consisted of a standard regimen of systemic antibiotics, local cooling and disinfection with KMnO4, and elevation of the lower extremity. There was no additional specific treatment of the ulcers, other stimuli of wound healing were excluded.

Results

In one case there was a total closure of the ulcers under the erysipelas (Fig. 1,  2). In two patients a reduction in size from 45 to 41.5 cm² and from 2.2 to 1.7 cm² occurred. In the fourth case only a subjective judgement of the reduction was taken. All ulcers became flatter. The concentrations of IL-6 and IL-2-receptor were initially raised and then later decreased in three of four cases (IL-6: case 1 from 177 to 73 pg/ml, case 2 from 66 to 28 pg/ml and case 3 from 342 to 117 pg/ml; IL-2-receptor: case 1 from 480 to 240 U/ml, case 2 from 1240 to 1020 U/ml and case 3 from 1360 to 950 U/ml).

Discussion

Because of the long-lasting existence and well known therapy resistance in each case, these changes suggest a positive effect of the erysipelas on the healing of the ulcers. We assume that serum cytokines could offer a possible explanation for this. The concentrations of the IL-6 and IL-2-receptor were initially raised and then later decreased in three of the four cases. In comparison to another eight patients with erysipelas but without ulcers who were treated in the same manner, the courses of interleukins were similar. In a control group consisting of 6 patients with ulcus cruris without erysipelas the IL-6 concentration was in normal region, in three cases the concentration of IL-2-receptor was increased. We therefore assume that the local infection could represent the trigger for cytokine activation at least concerning the IL-6 concentration, regardless of whether penetrating through a chronic ulcer or through a minor skin lesion. Because of the complex stimulation and regulation mechanisms in the cytokine network which are triggered by inflammation, systemic and local effects of keratinocytes, monocytes/macrophages, fibroblasts and endothelium cells could also be assumed to support wound healing [1-3]. On the other hand it is well known that chronic wounds themselves already express increased levels of cytokines. In our control group of patients with ulcus cruris without erysipelas we found elevated levels of IL-2-receptor in 50% of them. Due to the small number of cases the conclusions are somewhat limited. Furthermore, the presence of certain cytokines in the serum does not prove a local effect, and on the other hand, local processes are not always systematically identifiable [4]. Further relevant factors (varicosis, atherosclerotic occlusive disease, etc.) are mostly unaffected by the processes described and remain as underlying disorders.
Our clinical observation and the first orientating measurement of cytokines should encourage more systemic research concerning the generation of cytokines under the influence of a stimulating microbial antigen and the possible therapeutic benefit for the improvement of wound healing. n

References

1. Sugawara T, Gallucci RM, Simeonova PP, Lustre MI. Regulation and role of interleukin 6 in wounded human epithelial keratinocytes. Cytokine 2001; 15: 328-36.

2. Chu AC, Morris JF. The Keratinozyte. In: Bos JD, ed. Skin Immune System (SIS). 2^nd ed. Boca Raton: CRC Press LLC, 1997: 43-54.

3. Korge B, Smola H. Mechanismen der normalen Wundheilung. Z Hautkrhtn 1999; 7: 635-40.

4. Holzheimer RG, Steinmetz W. Local and systemic concentrations of pro- and anti-inflammatory cytokines in human wounds. Eur J Med Res 2000; 8: 347-55.