Title: Neurogenic Factors in the Impaired Healing of Diabetic Foot Ulcers
Authors: Hanna Galkowska, Ph.D., Waldemar L. Olszewski, M.D., Ursula Wojewodzka, M.Sc., Gregorz Rosinski, M.D., and Waldemar Karnafel, M.D.
Source: Journal of Surgical Research 2006; 134: 252 – 258.
PODIATRIC RELEVANCE:
Diabetes is a leading cause of lower extremity amputations, as a result of both neurologic and vascular complications. Diabetic peripheral neuropathy (DPN) includes sensory, distal, and symmetric polyneuropathy that may coexist with autonomic neuropathy. According to the authors, severe denervation exists in the skin of diabetics with active diabetic foot ulcers (DFUs), both sensory neuropathic and nonneuropathic.
METHODS:
The margin of the ulcer and surrounding intact skin of 20 patients (14 male and 6 female; 8 neuropathic and 12 nonneuropathic) with NIDDM and noninfected, active DFUs (Wagner Grades 2 – 4) were examined according to skin innervation, neuropeptides, expression of neurotrophins, and infiltration of immune cells into the tissues of DFUs. Testing for DPN included the use of a 5.07 SWM and a 128 Hz tuning fork. Biopsies were taken from the margins and surrounding intact skin of DFUs. Slides were stained, incubated, washed, incubated, again, with specific antibodies, and counterstained. Differences between neuropathic and nonneuropathic patient groups were determined by the Monte Carlo permutation exact test.
RESULTS:
This study established the existence of severe skin denervation in both sensory neuropathic and nonneuropathic NIDDM patients with active DFUs. It demonstrated the marked reduction of PGP 9.5+ nerves in the epidermis and adjacent skin of neuropathic diabetics, and confirmed that skin denervation was also found in NIDDM patients with nonsensory neuropathic DFUs. GAP 43 immunoreactive fibers in the dermis of all specimens of DFUs was seen when PGP95+ and SP+ skin innervation was decreased, suggesting the potential of sensory, autonomic, peripheral nerves in the skin of DFUs to regenerate. No statistically significant difference was found in inflammatory cells, procollagen type 1 producing fibroblasts, and a-smooth muscle actin+ fibroblasts between groups. The difference in expression of SP, CGRP, NGF, and concentration of leukocytes and fibroblasts in both groups was insignificant. The difference in the level of skin denervation between neuropathic or ischemic DFUs was negligible. Between neuropathic and nonneuropathic patients, no significant variation in the immune cell phenotypes of the skin was found.
COMMENTS:
The podiatric community has traditionally considered the underlying issues regarding DFUs to be based on either neuropathic or ischemic factors. The authors suggest that a decrease in the expression of neurogenic factors might cause a decreased concentration of immune cells and diminished granulation tissue formation, and that regardless of the neuropathic or ischemic nature of a DFU, the level of peri-ulcer skin denervation in both is essentially the same.
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Disclaimer:
Scientific Abstract Monthly postings are submitted by podiatric surgical residents. The ideas presented are not the opinions of the American College of Foot and Ankle Surgeons (ACFAS), nor are they presented as facts. ACFAS presents this information without any warranty of any kind, expressed or implied, and is not liable for its accuracy nor for any loss or damage caused by the user's reliance on information obtained in these areas.