Lower Limb Nonhealing Ulcers Associated With Chronic Diabetes: A Case Series

Introduction. Chronic, nonhealing skin ulcers of the lower limbs associated with diabetes pose a clinical challenge as their treatment requires more sophisticated and delicate approaches than in patients without diabetes. Objective. Herein, the authors demonstrate and discuss the implementation of their use of topical traditional Chinese medicines in several sample cases of lower limb nonhealing ulcers in patients with diabetes. Materials and Methods. A series of diabetic ulcer cases were treated with various approaches. First, the approach employed with each patient was determined based on ulcer location, depth, inflammatory extent, and local circulation. Next, an exploratory incision was performed to evaluate eschar condition. Finally, the therapy applied was modified depending on specific case characteristics. Results. The primary therapeutic approaches employed were: (1) selective partial ablation, including fenestration and encroachment; (2) debridement, which avoids secondary injury when local circulation is good; and (3) the turning-over method, in which necrotic tissue is cleaned down to the basal layer via application of a topical Chinese medicine that reduces inflammation and promotes chronic ulcer healing. Conclusions. These therapeutic approaches alleviated local inflammatory damage and adverse systemic reactions, which is an important basis for further treatment (eg, anti-infection treatment, blood glucose reduction, blood pressure control, organ function improvement, circulation promotion, and nutritional support). 

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Over the past few decades, type 2 diabetes mellitus (T2DM) has become a common health condition, with about 370 million people currently diagnosed with this disorder throughout the world.¹ Chronic, nonhealing leg ulcers associated with T2DM have become a major issue for those with diabetes. In China, diabetes has a morbidity of about 10% and has become the leading cause of chronic, nonhealing skin ulcers.² Elevated blood glucose levels due to diabetes damage small blood vessel endothelial cells, promote the arteriosclerosis of main arteries, and induce peripheral neuropathy. These impairments lead to the development of various chronic, nonhealing ulcers, which manifest primarily on feet.³ Foot ulceration, the most common cause of nontraumatic amputation, is a severe diabetic complication and can have severe effects on the quality of life of patients with T2DM.⁴ 

Diabetic foot ulceration (DFU) has 2 primary risk factors besides infection, both of which are sequelae of hyperglycemia: peripheral neuropathy and vasculopathy. Lower limb peripheral neuropathy disrupts sensory nerve transmission and impairs function. Vasculopathy of the lower limbs causes circulatory disorders of the feet, which slows or prevents wound healing and enables infections to take hold and spread. 

The primary clinical grading methods used to diagnose diabetic ulcers are: (1) the Wagner grading system (grades 0–5), which describes ulcer depth and signs of osteomyelitis or gangrene; and (2) the University of Texas Diabetic Foot Ulcer Classification System, which describes ulcer depth (grades 1–3) as well as the occurrence of ischemia and infection (stages A–D).^5,6 Although the University of Texas system indicates the simple presence of absence of ischemia, neither grading system addresses ischemia degree, thus limiting their clinical applications. Recently, the Society for Vascular Surgery Lower Extremity Guidelines Committee published a classification system for threatened lower limbs, categorizing and grading (0–3) 3 major risk factors of amputation: wound, ischemia, and foot infection (WIfI).⁷ 

The first step of the therapeutic process typically utilized to treat diabetes-related ulcers is wound bed preparation,^5,6 which facilitates wound healing. The primary steps involved in bed preparation include continuous debridement, exudate clearance, and adjustment of dysbacteriosis. Currently, a series of debriding methods have been developed, including autolytic debridement,⁸ conservative sharp and surgical debridement,⁹ enzymatic debridement,¹⁰ mechanical debridement, biodebridement,¹¹ chemical debridement,¹² and combinatory debridement.¹³ The debridement approach is based, in principle, on the moist wound environment theory,¹⁴ which purports the transformation of a chronic wound to an acute wound. Unfortunately, even with multidisciplinary cooperative treatments, such as pediatrics, vascular surgery, infectious disease, and sometimes plastic surgery, DFUs may not always result in satisfactory healing.

Eschar is a dry, coagulative mixture of seriflux, sanies, blood, necrotic tissues, and wound chemicals that can develop from ischemic necrosis of the epidermis and skin corium. Although incrustation is an important pathological process during the healing of chronic, nonhealing wounds, the therapeutic methods used to manage eschar development have not been described in the literature previously.

The Beijing Hospital of Traditional Chinese Medicine (Beijing, China) has gathered rich clinical and theoretical experiences regarding chronic, nonhealing ulcers, especially related to the use of traditional Chinese medicine therapies for diabetic chronic ulcers^15-26 (eg, the authors mainly treat chronic diabetic foot wounds with 3 methods of myogenic muscles: Zise Juchuang Ointment, Huiyang Shengji Ointment, and Zhuhong Ointment). In the authors’ experience, the proper management of eschar is crucial for the healing of chronic, nonhealing wounds. In this article, the authors summarize the common and effective therapeutic approaches used at Beijing Hospital of Traditional Chinese Medicine to treat the various types of eschars that form in chronic, nonhealing wounds, including debridement, fenestration or encroachment, and the turning-over method.

Clinical cases
All included cases involved patients who underwent ulcer surgery at Beijing Hospital of Traditional Chinese Medicine between January 2013 and January 2015. The research procedure was reviewed and approved by the ethics committee of Beijing Hospital of Traditional Chinese Medicine, and all patients provided written informed consent. Revascularization was not performed in the present cases due to various reasons, including counterindications and patient refusal.

Local ulcer processing
First, the depth and degree of the infection were determined based on the Infectious Diseases Society of America (IDSA) classification scheme for diabetic foot infections.² Eschar with fluctuations or severe purulent exudation was considered a reliable sign of severe infection. Because signs of systemic inflammation reactions do not emerge in some patients, the authors used systemic reaction as only a secondary method for detecting inflammation. Skin redness and swelling show a wide range of severity. Infections were considered superficial when redness and swelling were confined to the epidermis and were considered deep when redness and swelling reached deep structures (eg, nerves and fascia).

To determine the degree of ischemia associated with the ulcer, transcutaneous oxygen was measured, ankle-brachial index was applied, and leg arteries were assessed in a color Doppler ultrasound examination. These assessments, however, do not provide a complete representation of the local microcirculation. The following conditions were taken as signs of severe ischemia of the ulcer: (1) white, flush, dull-red, or cyanotic skin; (2) shiny, thin, and tight skin with a lowered temperature; and (3) severe pain. In addition, a dry, firmly adhered eschar without fluctuation that was black, dark red, or white in color was described as an ischemic necrotizing eschar. In contrast, the opposite conditions (ie, skin of normal color, thickness, elasticity, and temperature) were interpreted as indicating a low degree of ischemia.

Diabetic ulcers were monitored closely throughout the treatment process to detect signs of aggravation. Wound eschar was excised to fully drain the wound. The excision parameters were determined based on the observed local conditions and anatomical structures. 

Local treatment methods
In the treatment descriptions herein, fenestration refers to eschar incision from the middle outwards to promote drainage, encroachment refers to gradual excision of the peripheral eschar, and turning-over refers to topical application of warm (according the Traditional Chinese Medicine notion) herbs intended to promote ulcer healing and eschar formation. For wounds that had large-area eschars or that were severe (deep) enough to involve basilar ischemia (even in a small area), the authors used fenestration to facilitate drainage and prevent the spread of infection (Figure 1). For severe wounds with basal ischemia, they used encroachment to avoid wound expansion and iatrogenic injury and the turning-over method to limit local inflammatory responses and to promote healing (Figure 2). In addition, they utilized debridement to eliminate unwanted tissue when substrate conditions permitted. 

Patient age, sex, and medical history are presented in Table 1. In Table 2, the biochemical test results and imaging findings of the reported patients are described.

Case 1: toe ulcer
A 60-year-old man presented with necrosis of the left fifth digit measuring 4.5 cm x 4.0 cm x 0.5 cm. The skin surrounding a severe ulcer on the fifth digit was dull-red and cool to touch (Figure 3A), indicating severe ischemia; however, inflammation was confined to the ulcer. The authors classified the ulcer as IDSA mild with a WIfI clinical stage score of 2 (wound 2, ischemia 1, and foot infection 2). They first excised the edge of the eschar and purulent secretion was observed, indicating the presence of an under-eschar infection. Due to infection, the gangrenous fifth digit was excised to prevent the infection from spreading to the other toes. 

Next, they used encroachment methods to excise the eschar with wound drainage together with basic symptomatic treatment (ie, topical antibiotic, blood glucose reduction, blood pressure modulation, organ function support, circulation promotion, and nutritional support). On day 28 (Figure 3B), a clear dividing line between the eschar and the surrounding skin was observed. The granulation tissue on the surface of the ulcer began to proliferate modestly, and the temperature of the surrounding skin returned to normal. On day 81, the gangrenous fifth digit was amputated, and 10 days after the operation, granulation tissue was proliferating gradually on the surface of the wound with thick secretions (Figure 3C). After 3 weeks, healthy granulation tissue reddened with obvious signs of healing (Figure 3D). The wound healed completely 8 months after the amputation of the fifth digit.

Case 2: central foot ulcer
An 82-year-old man presented with a large ulcer measuring 9.5 cm x 5.5 cm x 0.4 cm affecting the dorsal left foot and the second and third toes; the ulcer was complicated with an acute under-eschar infection and low-degree ischemia (Figure 4A). The ulcer was classified as IDSA moderate with a WIfI clinical stage score of 4 (wound 3, ischemia 1, and foot infection 2). The treatment goal was to avoid foot amputation. First, the entire eschar mass was excised, revealing purulent exudate that secreted from under the fascia (Figure 4B). The authors fenestrated the fascia layer, maintained wound drainage, and provided basic symptomatic treatment (previously described). Subsequently, the local inflammation and microcirculation impairment in the vicinity of the ulcer improved gradually (Figure 4C), creating favorable conditions for amputation of the toe and dermatoplasty of the dorsal of the foot (Figure 4D). Ultimately, improved distal circulation was observed after 4 months of treatment (Figure 4E). The wound healed completely in 1.5 years (Figure 4F).

Case 3: ankle ulcer
A 77-year-old man presented with a severe ulcer measuring 8.3 cm x 3.6 cm x 0.7 cm around the left medial malleolus. As shown in Figure 5A, the skin around the ulcer was red, swollen, infected, and cold, indicating severe ischemia. It was classified as IDSA moderate with a WIfI clinical stage of 4 (wound 1, ischemia 1, and foot infection 3). First, fenestration was performed on the fluctuating part of the eschar, and it was found that the infection had already affected the superficial corium; amputation becomes necessary if there is not sufficient corium to support healing. The authors utilized the encroachment method to excise the turn-up edge of the eschar with wound drainage and provided basic symptomatic treatment to improve local and systemic conditions. The inflammation caused by the infection resolved gradually. On day 14 (Figure 5B), most of the eschar was excised, the inflammatory exudation was limited, and the corium was found to be partially intact, indicating that wound healing was possible. On day 28 (Figure 5C), proliferating granulation tissue was noted on the surface of the wound, suggesting active healing. The wound was almost healed at 8 months (Figure 5D). 

Case 4: heel ulcer
A 69-year-old woman presented with a large lesion measuring 3.1 cm x 3.2 cm x 0.5 cm on the right heel. The skin surrounding the ulcer was dark red and of a normal temperature (Figure 6A), suggesting mild ischemia. The eschar was thin and tough, with significant fluctuation and under-eschar empyema. The ulcer was classified as IDSA mild with a WIfI clinical stage score of 4 (wound 1, ischemia 1, and foot infection 2). To avoid further inflammatory damage to the surrounding structures, the eschar was excised immediately and the purulent exudates were cleaned to prevent infection of the normal fatty tissue of the heel. The infective affected only the superficial corium, and the integrity of the corium largely was intact. After careful debridement and wound drainage, the inflammation resolved gradually (Figure 6B). In the subsequent treatment, granulation tissue proliferation was observed at the base of the wound, indicating healing (Figure 6C, D). After 412 days of treatment, the wound healed (Figure 6E).

Case 5: crus ulcer
A 56-year-old man presented with an ulcer measuring 4.5 cm x 3.7 cm x 0.4 cm on the posterior tibial skin with fine local circulation (Figure 7A). The eschar was black and thick with significant fluctuation. The skin surrounding the ulcer was red and swollen and severely infected with purulent exudates when pressure was applied to the eschar. These conditions indicated the ulcer could potentially heal. It was classified as IDSA moderate with a WIfI clinical stage score of 1 (wound 1, ischemia 0, and foot infection 3). The entire eschar was excised immediately, and the drainage of the under-eschar empyema were cleaned (Figure 7B). On day 36, proliferating granulation tissue was observed at the base of the ulcer (Figure 7C), and the ulcer healed 3 months later.

Eschar is a pathological product that develops during the wound healing process. There are different forms of eschars that can be characterized by a variety of features. Based on the texture, eschars can be divided into the following categories: eschar (Figure 3A), tough (Figure 5A), soft (Figure 1A), and putrid (Figure 6B). When pressed, the eschar may exhibit floating (Figure 7A), undulation (Figure 1A), flexibility (Figure 4A), or solidness (Figure 2A). The color of eschar is determined by the components that it is comprised of, such as yellow for serous eschars, green-yellow for purulent eschars, dark red for eschars with blood, and white for ischemic eschars. Eschar color also can be affected by the inclusion of chemicals. The eschar boundaries may be clear, cloudy, or opaque with regular, less regular, or irregular edges. The eschar surface may be smooth, rough, flat, bumpy, or concave. Furthermore, eschars may form different shapes such as mammilla-like, cauliflower-like, or hemispheric. The contents under the eschar may include blood, seriflux, purulence, sebum, or cutin. Eschars may be singular; multiple arranged in a line, band, or circle; or irregular multiple areas. During eschar palpation, the size, shape, thickness, firmness, and fluctuation of the eschar are examined in addition to local skin temperature, local adhesion, pressing pain, and paresthesia. Here, the authors discuss the therapeutic approaches employed to treat eschars at their center.

Gradual eschar excision therapy for toe ulcers
Because the corium layer of toe skin is thin and rich with underneath structures, infection can easily spread from the toes to the central part of the foot (Figure 3A). If the degree of under-eschar infection cannot be determined, a fenestration or excision of the turn-up edge of the eschar may help; if combined with drainage and symptomatic treatment, the infection can often be confined. If the under-eschar infection only has small amounts of purulent exudates, an expanded debridement is unnecessary; however, these cases can evolve into dry gangrene and coexist on the toe for a prolonged period. Fenestration may be the best choice for patients with poor systemic conditions or patients who refuse amputation. Furthermore, fenestration prepares the patient for further interventional procedures or amputation. 

Immediate eschar excision for central foot ulcers
The subcutaneous tissues of the central foot, such as muscle, tendon, and fascia, are loosely arranged and the blood supply is rich because of the arcus arteria dorsalis pedis. This anatomy enables the spread of infection through the tissue space. The primary purpose of treatment is to maintain drainage and thereby prevent the spread of infection, avoiding amputation. 

As shown in Figure 4A, ulcers can be affected by moist gangrene. To confine the infection and stop necrosis expansion in such cases, the authors excised the entire eschar with drainage, which should limit local inflammatory damage and the systemic inflammatory impacts, such as excessive inflammatory consumption and septic reaction. Wound drainage prevents inflammatory damage to tissues around the ulcer and prevents further inflammatory invasion. When moist gangrene is present, amputation should be considered to eliminate risks to the patient’s life. 

In case 2, the inflammation resolved gradually, and granulation tissue proliferated at the base of the ulcer, which created favorable conditions for further treatment. Conversely, in case 1 (Figure 3A), the turn-up edge of the eschar was excised, and the eschar was firmly adhered to subcutaneous tissue without inflammation and exudation. If the entire eschar had been excised immediately, the ulcer would have had a higher chance of infection, potentially leading to aggravation of the ischemia and expansion of inflammation, thus possible urgent amputation. 

Precise eschar excision for ankle ulcers
The ankle is a junction between the foot and the tibia and fibula as well as an aggregate region of tendons. Ankle skin is thin, and the corium layer makes direct contact with bones without any subcutaneous tissues. Therefore, an ulcer infection can spread easily, destroy the joint capsule and bones, and may even cause osteomyelitis, all strong risk factors for amputation. 

In case 3 (Figure 5A), the authors first excised the edge of the eschar and found the inflammatory damage was relatively superficial. After precise eschar excision with drainage, the infection resolved and the wound healed. The ulcer in case 1 (Figure 3A) also was superficial but was complicated by severe ischemia and poor local circulation. To treat this patient, the eschar was excised gradually, the wound was kept dry, and the ulcer was allowed to coexist on the toe for a prolonged period. If the entire eschar had been excised immediately, the wound would have been expanded. In addition, the local ischemia would have worsened, potentially leading to further damage.

Conservative treatment for heel ulcers
The skin of the heel is thin, but the subcutaneous space is filled with a thick layer of fatty tissue. If infection from the ulcer invades the fatty tissue, rapid necrosis of the entire layer occurs, which destroys the calcaneus and can even cause osteomyelitis (primary amputation risk factors).

The ulcer in case 4 (Figure 6A) was severely ischemic with poor local circulation, which limited the infection. The ulcer was treated with basic symptomatic treatment to improve local blood circulation rather than excising the eschar immediately. When the local circulation improved, the authors began to excise the eschar gradually. 

Therapeutic approaches for crus ulcers
The treatments utilized for pretibial and posterior tibial ulcers are different. Because the blood supply of the posterior tibial region is rich, and the subcutaneous tissue is thick, posterior tibial ulcers can heal easily following excision with drainage (Figure 6A). On the other hand, the subcutaneous tissue of the pretibial region is thin, indicating the eschar should be excised with care to prevent bone damage. 

In case 5, the eschar was excised gradually and the wound was kept dry, allowing the ulcer to coexist on the crus for a prolonged period of time.

Debridement
Before debridement, the treatment goals must be determined based on the degree of local ischemia and infection as well as ulcer location. When amputation cannot be avoided, an enlarged debridement is needed to drain necrotic tissue and prevent a systemic reaction in preparation for amputation. If amputation is not considered to be an option, debridement should be limited to providing wound drainage. In the event that the infection invades the surrounding tissue or shows signs of spreading, debridement should be limited to the wound area because the necrotic tissue may provide a barrier that can confine the injury.

As this article summarizes the experiences of treating chronic wounds in diabetes, the treatment may not meet the opinions of others. This paper included a lack of control group, a small sample size, and a single institutional design.

Treating patients with diabetes who have chronic wounds is challenging and multifactorial. As shown herein, the authors’ systematic, yet individualized, treatment methods for the various forms of eschar-forming ulcers were effective. Specifically, they reduced infection severity, improved circulation, and reduced pain. Nevertheless, in case 2, the infection recurred later, perhaps due to excessive walking and irregular dressing changes, and an above-knee amputation was necessary to save the patient’s life.

The authors developed a systematic methodology for the treatment of various eschar conditions associated with lower limb ulcers. Based on their experience, particularly with the 5 cases included in this report, they have developed a couple recommendations. First, wound healing requires good blood supply, but improving blood circulation can be a lengthy process. Therefore, in cases with poor local circulation, they recommend a systematic approach involving pain control, quelling of any local infection, and reducing the span of the ulcer, thus providing time for blood circulation to improve. Second, basal tissue treatment, daily care, and surgical treatment should be combined in the whole treatment process. The entire therapeutic process should involve the collaboration of a multidisciplinary team. Protecting patients’ lives and maximizing their quality of life are the ultimate aims; in some cases, the best outcome may be survival with a long-term chronic wound. 

Authors: Guangyu Wang, MD; Yu Wang, MD; Fusheng Wang, MD; Yi Ding, MD; Yudong Kang, MD; Yu Dong, MD; Peiwen Lv, MD; and Xuying Xu, MD

Affiliation: Department of Chinese Medicine Surgery, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China

Correspondence: Xuying Xu, MD, Department of Chinese Medicine Surgery, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China; xxying7341@126.com

Contributions: This study was designed and the manuscript written principally by Guangyu Wang under the guidance of professor Peiwen Lv. Guangyu Wang and Yu Wang collected the patients’ basic clinical information, conducted the follow-up examinations, and took pictures of the ulcers. Xuying Xu, Fusheng Wang, Yi Ding, and Yudong Kang selected the patients and provided descriptions of the ulcers and clinical treatments. All work was conducted under the guidance of Peiwen Lv. Professor Lv decided upon the therapeutic protocols for the ulcers and assisted with manuscript writing.

Disclosure: This study was supported by grants from the Beijing Municipal Administration of Traditional Chinese Medicine (WZF2012-13), National Natural Science Foundation (81673975), Beijing Science and Technology Committee Capital Special Project (Z121107001012103), the Key Discipline of the State Administration of Traditional Chinese Medicine: Traditional Chinese Medicine Ulcers Epidemiology, National Clinical Key Specialty: Surgery of Chinese Medicine, the “Ten kinds of diseases and medicines” program of the Beijing Administration of Traditional Chinese Medicine (CYX2014-02), and Clinical Key Specialty of the State Administration of Traditional Chinese Medicine: Surgery. The authors disclose no financial or other conflicts of interest.