Ulcers of lower extremities are often resistant to therapy in diabetic patients. It has recently been reported that the activity of proteases is crucial in wound repair (1), but excessive protease activity can damage granulation tissue, delaying healing. It is noteworthy that protease activity is elevated in fluid from chronic, nonhealing wounds (1).
A recently described protease inactivator matrix (Promogram; Johnson & Johnson, Skipton, U.K.), composed of oxidized regenerated cellulose and collagen, has been shown to reduce elastase, plasmin, and metalloproteinase activity in chronic wound fluids of diabetic patients, stimulating wound repair process (1,2). Both of the components of this matrix, oxidized cellulose (3) and collagen (4), have been reported to accelerate the healing of diabetic foot ulcers.
We assessed the effects of this matrix in two diabetic patients with chronic foot ulcers. G.C., a 76-year-old man with a BMI of 34.9 kg/m2, type 2 diabetes of 26-year duration, and a previous myocardial infarction, was treated with metformin 2,550 mg/day. HbA1c was 7.5% (upper limit of normal 6.2%). The patient was also affected by hypertension (treated with enalapril and amlodipine) and untreated hypertriglicerydemia and hypercholesterolemia. The patient showed microalbuminuria, with normal creatinine levels, chronic neuropathy with increased vibratory perception threshold bilaterally, peripheral vascular disease (Winsor Index [ankle/arm blood pressure ratio] = 0.75 bilaterally) and a neuroischemic ulcer (3 cm × 4 cm; Wagner grade I) in the plantar region of the right foot. No dry necrolytic tissue was present, and granulation tissue was clearly detectable. Cultural examination of wound fluid did not identify any microorganism, and X-ray was negative for osteomyelitis. Despite standard wound care (surgery curettage and advanced medications) for 24 weeks, the lower-limb lesion did not show any relevant improvement. The matrix was applied twice a week, after the application of polyuretanic foam and hydrobenda. Improvement was noticeable after 3 weeks, with increase of granulation tissue and reduction of wound area. Healing was complete within 5 weeks from the beginning of treatment.
G.I., a 68-year-old woman, was affected by type 2 diabetes with a duration of disease 22 years; her BMI was 25.6 kg/m2. G.I. was treated with insulin (50 units/day in four administrations), with an HbA1c of 8.0%. She showed signs of neuropathy, with increased vibratory perception thresholds, and peripheral vascular disease (Winsor Index [ankle/arm blood pressure ratio] = 0.70 bilaterally). The patient also reported suboptimally controlled hypertension, chronic renal failure, chronic heart failure, and diabetic retinopathy. She showed an ulcer of the plantar region of the left foot (5 cm × 6 cm) with extensive necrosis, which was surgically removed. Staphylococcus α-hemolytic, Candida nonalbicans, and unidentified anaerobial bacteria were isolated from the lesion. For this reason, general treatment with teicoplanin, imipenem, and fluconazole was undertaken, and the infection eradicated within 3 weeks. An X-ray examination of the right foot did not show any sign of osteomyelitis. Despite standard wound care for 40 weeks, the lesion did not heal, although granulation tissue was present. Treatment with oxidized regenerated cellulose and collagen matrix twice a week, after the application of polyuretanic foam and hydrobenda, resulted in a complete healing within 12 weeks.
These two cases suggest that patients suffering from chronic wounds with delayed healing could benefit from this novel treatment, although randomized controlled trials specifically directed at diabetic patients with nonhealing foot ulcers of long duration are needed.
References
Address correspondence to Matteo Monami, Department of Critical Care Medicine and Surgery, Unit of Gerontology and Geriatrics, University of Florence and Azienda Ospedaliera Careggi, Via delle Oblate 4, 50139 Florence, Italy. E-mail: [email protected].
