Bioengineered Human Dermal Tissue Grafting of Necrobiosis Lipoidica Diabeticorum Ulcerations: A Case Series

A retrospective case series of sequential patients with recurrent ulcerations associated with necrobiosis lipoidica diabeticorum (NLD) is presented. Standard wound care required 40 ± 7.21 weeks to attain complete epithelialization. Standard wound care plus weekly applications of bioengineered neonatal human dermal tissue shortened healing to 7.14 ± 3.44 weeks.

Necrobiosis lipoidica diabeticorum (NLD) is a disorder characterized by atrophic, yellowed, and waxy appearing tissue with visible cutaneous vessels.¹ Histologically, NLD may demonstrate small-vessel vasculitis initially progressing to a granulomatous disorder with collagen degeneration at the dermis and subcutaneous tissues.² Reported first in 1929, NLD remains enigmatic as to its etiology.³ With a 15% ulceration rate, this poorly understood disorder is a challenge for wound care teams.⁴   A recent case-based review of the literature listed the following as treatment options: cutaneous blood flow enhancers, steroid therapy, wound healing enhancers, immunomodulation, surgery, and miscellaneous topical medications. While all of these therapies did demonstrate some variable improvement in NLD, successful care of associated wounds remains variable.⁵ A single case report was published that indicated human fibroblast-derived dermal substitute (HDS) may have efficacy in treating these wounds by implantation of normal collagen and a host of dermal growth factors.⁶ A PubMed search of 200 articles dating back to 1989 yielded no articles listing standard wound healing rates for wounds associated with NLD.

A cohort of 6 patients with 7 recurrent NLD lower extremity ulcerations was identified at the author’s wound care center. All patients were previously diagnosed with NLD via physical and histological examination. The original NLD ulcerations were all treated with debridement, moist wound healing, and local steroids. The mean healing time of their previous ulcerations was 40 ± 7.21 weeks. Because of this prolonged healing time, these patients with recurrent NLD wounds were offered treatment with the HDS if their wounds were not responding to standard wound care.   Local Institutional Review Board approval was obtained. Pretreatment screening included ankle brachial index, pre-albumin level, basic metabolic profile, and complete blood cell count. Wound cultures were performed in the presence of clinical signs of infection, and appropriate antibiotic was administered prior to initiation of therapy.   The HDS was applied weekly in accordance with the dosage determined to be most efficacious in the healing of diabetic foot ulcers.⁷ Sharp debridement of all necrotic tissue was performed prior to each application.   Primary dressings were nonadherent mesh followed by absorbent gauze layers. The secondary gauze type dressings were changed after 48 hours and the primary nonadherent dressing was left in place for 1 week. Wound measurements and photographs were taken weekly. The mean time to complete wound epithelialization was then computed. Patients were subsequently followed for any sign of recurrent tissue breakdown.

Standard wound care was provided in the recurrent ulceration group for 6.29 ± 5.88 weeks prior to initiation of bioengineered living dermal tissue therapy. Failure to reduce the size of the wound by 50% at 4 weeks or 90% at 8 weeks lead to application of the HDS. Seven NLD wounds were treated with the HDS. The subsequent mean time to complete epithelialization was 7.14 ± 3.44 weeks. All treated wounds healed. Interestingly, the newly epithelialized wound had a visibly different appearance than the surrounding NLD affected skin. (Figure 1, Figure 2)   No adverse reactions to the treatment were encountered. The infection rate during the time of graft treatment was 0%, and there were no adverse events. No adjustment in the patients’ diabetes medications or general health care was made, and none of the patients required revascularization or nutritional supplementation. During a follow-up period of 4 weeks to 7 years, no recurrent breakdown of the wounds occurred.

Because there was previous experience treating NLD in this patient cohort, it seems reasonable that an inference can be made regarding standard wound care vs standard wound care with the addition of HDS. In the authors opinion, the comparison of 40 weeks to heal with standard wound care and just over 7 weeks to heal with the addition of HDS in the same patients warrants further objective investigation.   This rapid healing rate and visibly different appearance of the healed tissue leads the authors to suspect the HDS may provide some missing components of wound healing in NLD wounds. This engineered tissue is made of neonatal dermal fibroblasts layered onto a 3 dimensional bioabsorbable matrix. These metabolically active cells provide collagen types I and III, fibronectin, and tenacin, as well as glycosoaminoglycans and the host of growth factors found in healthy dermis. This may help alleviate the collagen degradation at the dermal and subcutaneous tissues found in NLD. Additionally, the living cells promote cell proliferation and angiogenesis differentiating this therapy from the “scaffolding-type” wound care matrices.

Biopsy of the healed wound may have provided some insight into the unique characteristics of the treated skin in comparison to the surrounding NLD. This was not performed. However, even with the limits of this case series, bioengineered living human dermal tissue appears to be a worthy partner in battling the difficult ulcerations found in NLD.

Andrew J. Rader, DPM, FACFAOM, FAENS, FAPWCA, FACCWS is from the Wound Care Center, Memorial Hospital and Healthcare Center, Huntingburg, IN; Indiana Foot & Ankle, Jasper, IN; and the Lower Extremity Research Institute, Huntingburg, IN. Megan Wilson, RN, CWCN is from the Wound Care Center, Memorial Hospital and Healthcare Center, Huntingburg, IN.

Address correspondence to: Andrew Rader, DPM Indiana Foot & Ankle 645 W. 5th Street Jasper, IN 47546 drajrader@gmail.com

Disclosure: The authors disclose no financial or other conflicts of interest.