Efficacy of Topical Insulin Therapy for Chronic Trophic Ulcers in Patients with Leprosy: A Randomized Interventional Pilot Study.

BACKGROUND: Chronic trophic ulcers (CTUs), especially those located over the plantar region, are a leading cause of deformity and disability in patients with leprosy. Despite the various treatment modalities available, CTUs can be chronic and refractory to treatment. The successful use of topical insulin in various types of wounds led researchers to evaluate its safety and efficacy in the treatment of plantar CTUs. METHODS: Forty-two patients who had completed a multidrug treatment for leprosy were recruited and randomized into two groups. In the test group, 23 patients received 10 units (0.1 mL) of topical insulin (Actrapid) in 1 mL of normal saline twice daily over treated areas. The placebo group (n = 19) received topical normal saline only. The primary end point was the proportion of patients with complete wound closure by 12 weeks. Secondary end points included time to healing, wound area reduction, Physician Global Assessment of Efficacy scores, and Dermatology Life Quality Index scores at the end of 12 weeks. RESULTS: The majority of CTUs (80%) were situated over the forefoot; the metatarsal head of the hallux was the most common site (86%). Wound healing was faster (0.61 ± 0.31 vs 0.14 ± 0.42 cm per week, P < .0001), and the number of days to complete healing was significantly shorter in the test group compared with the placebo group (31.5 ± 17.6 vs 44.3 ± 16.2 days, P = .02). The only observed adverse effect in the test group was white granular deposits over the CTU (n = 10). CONCLUSIONS: Topical insulin therapy may be a safe, efficacious, cheap, and easily available treatment option in CTUs among patients with leprosy.

The bacteriostatic effect of controlled-flux electrolyzed acidic solution on healthy hallucal skin.

BACKGROUND: There are various treatment protocols to manage the increased bacterial load in plantar ulcers. Recently, Controlled-Flux Electrolyzed Acidic Solution (CFEAS), with a pH less than 3, has appeared to be an effective option since its antimicrobial effect could help in the healing of those ulcers. In order to evaluate its potential in this sense, the aim of the present study was to compare bacterial growth on healthy hallucal skin using two types of bandaging (control and Controlled-Flux Electrolysed Acidic Solution). MATERIAL AND METHODS: In a sample of 19 healthy subjects, two experiments were performed. In the first, for each subject, two identical hallux bandages were applied in the early morning. At random between left and right foot, either physiological saline (wetting every 2 h) was applied or nothing (control). In the second, two days later, new bandages were applied as before, but now either wetting with Controlled-Flux Electrolysed Acidic Solution (experimental, again wetting every 2 h) or nothing (control). In each experiment, the bacterial load in the nail fold was assessed at the first moment and after 10 h from standard counts of bacterial colony forming units (CFU). RESULTS: In the first experiment, the CFU counts had increased significantly (p < 0.05) in both toes after the 10-h period. In the second experiment, while the bacterial load increased significantly (p = 0.001) from 0.68 ±â€¯0.8 × 104 CFU/cm2 (the "pre" sample) to 1.3 ±â€¯0.9 × 104 CFU/cm2 (the "post" sample) in the control toe, in the experimental CFEAS toe, the pre sample bacterial load was 0.61 ±â€¯0.6 × 104 CFU/cm2, and the post sample 0.9 ±â€¯0.8 × 104 CFU/cm2, with no significant difference between them (p = 0.221). Negative cultures were obtained in 3 cases (15.78%) of the experimental toe post sample, and equal post and pre counts in 2 cases (10.5%). CONCLUSION: Controlled-Flux Electrolyzed Acidic Solution has an effect on healthy hallucal skin that is bacteriostatic, and in some cases bactericidal. This effect could be very helpful in treating plantar ulcers when there is a greatly increased bacterial load in the wound, thus potentially favoring the normal formation of granulation tissue in the skin and normal healing and closure of the ulcer.

The beneficial effect of traditional Japanese herbal (Kampo) medicine, Hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang), for patients with chronic wounds refractory to conventional therapies: A prospective, randomized trial.

Hochu-ekki-to (HET) is a traditional Japanese herbal (Kampo) medicine for the treatment of severe weakness, loss of appetite, and indigestion in elderly patients and for the prevention of opportunistic infections. The impact of HET on patients with chronic wounds refractory to conventional therapies was investigated in a prospective, randomized trial, including 18 patients divided into medication (7.5 g oral HET per day, n = 9) and control (n = 9) groups. Wound healing during the 12-week study period was scored based on depth, exudate, size, inflammation/infection, granulation tissue, necrotic tissue, and pocket size. At 12 weeks, wound healing progressed in all nine patients in the medication group, whereas wound healing progressed in only three patients in the control group (significant difference, p < 0.01; relative risk: 3.00). In the medication group, the total score decreased significantly at 8 weeks and later. To the best of our knowledge, this study was the first to show that HET promoted the healing of chronic wounds resistant to conventional treatments. HET may be a choice as an adjunctive therapy for chronic wounds, particularly for patients with malnutrition. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031620).

The Management of Critically Colonized and Locally Infected Leg Ulcers with an Acid-Oxidizing Solution: A Pilot Study.

OBJECTIVE: Critical colonization or local infection is very common in chronic wounds, but clinically problematic. Because therapeutic options for these conditions are limited in number and efficacy, the study authors tested a new acid-oxidizing solution (AOS [Nexodyn]; APR Applied Pharma Research S.A., Balerna, Switzerland) to determine its ancillary antimicrobial properties and potential support for wound healing. DESIGN AND SETTING: This open-label clinical case series was conducted with a prospective, single-arm design at the Federal County Hospital in Bregenz, Austria. PATIENTS: In the study, 30 patients with critically colonized or locally infected chronic leg ulcers of any origin were included. INTERVENTIONS: The AOS was applied on each leg ulcer at every dressing change for 35 days. MAIN OUTCOME MEASURES: The tolerability and performance of the AOS were assessed by evaluating the ulcer characteristics and comparing them with those at baseline. The clinical course of wounds was analyzed using standard measures for bioburden, local infection, pain, pH, and wound healing. MAIN RESULTS: Application of the solution was well tolerated, and no adverse events were recorded. In all patients, local infection was overcome, and wound bed pH and wound area decreased significantly. In addition, patient pain levels decreased to a level where interventions were not required after study day 7. In 37% of all patients, a complete resolution of chronic ulcers was achieved by the end of the study period. CONCLUSION: According to these results, the AOS seems to be a valid and highly tolerable treatment to support wound healing in locally infected ulcers. Nevertheless, larger controlled cohort studies are needed to substantiate these findings.

Implications of Antimicrobial Combinations in Complex Wound Biofilms Containing Fungi.

Diabetic foot ulcer treatment currently focuses on targeting bacterial biofilms, while dismissing fungi. To investigate this, we used an in vitro biofilm model containing bacteria and fungi, reflective of the wound environment, to test the impact of antimicrobials. Here we showed that while monotreatment approaches influenced biofilm composition, this had no discernible effect on overall quantity. Only by combining bacterium- and fungus-specific antibiotics were we able to decrease the biofilm bioburden, irrespective of composition.

Topical antimicrobial agents for treating foot ulcers in people with diabetes.

BACKGROUND: People with diabetes are at high risk for developing foot ulcers, which often become infected. These wounds, especially when infected, cause substantial morbidity. Wound treatments should aim to alleviate symptoms, promote healing, and avoid adverse outcomes, especially lower extremity amputation. Topical antimicrobial therapy has been used on diabetic foot ulcers, either as a treatment for clinically infected wounds, or to prevent infection in clinically uninfected wounds. OBJECTIVES: To evaluate the effects of treatment with topical antimicrobial agents on: the resolution of signs and symptoms of infection; the healing of infected diabetic foot ulcers; and preventing infection and improving healing in clinically uninfected diabetic foot ulcers. SEARCH METHODS: We searched the Cochrane Wounds Specialised Register, CENTRAL, Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus in August 2016. We also searched clinical trials registries for ongoing and unpublished studies, and checked reference lists to identify additional studies. We used no restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA: We included randomised controlled trials conducted in any setting (inpatient or outpatient) that evaluated topical treatment with any type of solid or liquid (e.g., cream, gel, ointment) antimicrobial agent, including antiseptics, antibiotics, and antimicrobial dressings, in people with diabetes mellitus who were diagnosed with an ulcer or open wound of the foot, whether clinically infected or uninfected. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, 'Risk of bias' assessment, and data extraction. Initial disagreements were resolved by discussion, or by including a third review author when necessary. MAIN RESULTS: We found 22 trials that met our inclusion criteria with a total of over 2310 participants (one study did not report number of participants). The included studies mostly had small numbers of participants (from 4 to 317) and relatively short follow-up periods (4 to 24 weeks). At baseline, six trials included only people with ulcers that were clinically infected; one trial included people with both infected and uninfected ulcers; two trials included people with non-infected ulcers; and the remaining 13 studies did not report infection status.Included studies employed various topical antimicrobial treatments, including antimicrobial dressings (e.g. silver, iodides), super-oxidised aqueous solutions, zinc hyaluronate, silver sulphadiazine, tretinoin, pexiganan cream, and chloramine. We performed the following five comparisons based on the included studies: Antimicrobial dressings compared with non-antimicrobial dressings: Pooled data from five trials with a total of 945 participants suggest (based on the average treatment effect from a random-effects model) that more wounds may heal when treated with an antimicrobial dressing than with a non-antimicrobial dressing: risk ratio (RR) 1.28, 95% confidence interval (CI) 1.12 to 1.45. These results correspond to an additional 119 healing events in the antimicrobial-dressing arm per 1000 participants (95% CI 51 to 191 more). We consider this low-certainty evidence (downgraded twice due to risk of bias). The evidence on adverse events or other outcomes was uncertain (very low-certainty evidence, frequently downgraded due to risk of bias and imprecision). Antimicrobial topical treatments (non dressings) compared with non-antimicrobial topical treatments (non dressings): There were four trials with a total of 132 participants in this comparison that contributed variously to the estimates of outcome data. Evidence was generally of low or very low certainty, and the 95% CIs spanned benefit and harm: proportion of wounds healed RR 2.82 (95% CI 0.56 to 14.23; 112 participants; 3 trials; very low-certainty evidence); achieving resolution of infection RR 1.16 (95% CI 0.54 to 2.51; 40 participants; 1 trial; low-certainty evidence); undergoing surgical resection RR 1.67 (95% CI 0.47 to 5.90; 40 participants; 1 trial; low-certainty evidence); and sustaining an adverse event (no events in either arm; 81 participants; 2 trials; very low-certainty evidence). Comparison of different topical antimicrobial treatments: We included eight studies with a total of 250 participants, but all of the comparisons were different and no data could be appropriately pooled. Reported outcome data were limited and we are uncertain about the relative effects of antimicrobial topical agents for each of our review outcomes for this comparison, that is wound healing, resolution of infection, surgical resection, and adverse events (all very low-certainty evidence). Topical antimicrobials compared with systemic antibiotics : We included four studies with a total of 937 participants. These studies reported no wound-healing data, and the evidence was uncertain for the relative effects on resolution of infection in infected ulcers and surgical resection (very low certainty). On average, there is probably little difference in the risk of adverse events between the compared topical antimicrobial and systemic antibiotics treatments: RR 0.91 (95% CI 0.78 to 1.06; moderate-certainty evidence - downgraded once for inconsistency). Topical antimicrobial agents compared with growth factor: We included one study with 40 participants. The only review-relevant outcome reported was number of ulcers healed, and these data were uncertain (very low-certainty evidence). AUTHORS' CONCLUSIONS: The randomised controlled trial data on the effectiveness and safety of topical antimicrobial treatments for diabetic foot ulcers is limited by the availability of relatively few, mostly small, and often poorly designed trials. Based on our systematic review and analysis of the literature, we suggest that: 1) use of an antimicrobial dressing instead of a non-antimicrobial dressing may increase the number of diabetic foot ulcers healed over a medium-term follow-up period (low-certainty evidence); and 2) there is probably little difference in the risk of adverse events related to treatment between systemic antibiotics and topical antimicrobial treatments based on the available studies (moderate-certainty evidence). For each of the other outcomes we examined there were either no reported data or the available data left us uncertain as to whether or not there were any differences between the compared treatments. Given the high, and increasing, frequency of diabetic foot wounds, we encourage investigators to undertake properly designed randomised controlled trials in this area to evaluate the effects of topical antimicrobial treatments for both the prevention and the treatment of infection in these wounds and ultimately the effects on wound healing.

Low-Molecular-Weight Heparins as Immunomodulators in Dermatology Practice.

Low-molecular-weight heparins (LMWHs) have some effects on cell proliferation and inflammation beyond mere anticoagulation. They have been tried on treatment of a few dermatological disorders such as lichen planus, skin wound healing, recurrent aphtous stomatitis, chronic urticaria, and contact hypersensitivity. LMWHs are generally well-tolerated drugs, rarely can lead to severe reactions. In this article, we will review the novel indications of LMWHs in dermatology practice and common skin reactions associated with their use.

Successful Treatment With Bosentan for Digital Ulcers Related to Mixed Cryoglobulinemia: A Case Report.

A 49-year-old man diagnosed with genotype 1 hepatitis C, CD5-positive marginal zone lymphoma, and mixed cryoglobulinemia type II developed skin ulcers and necrosis in his right foot. He was treated with amlodipine, corticosteroids, plasmapheresis, alprostadil, rituximab, and cyclophosphamide without a satisfactory response. For this reason, he required a partial amputation of the second, third, and fifth fingers of the right foot. To prevent ulcer deterioration of the first finger, bosentan was initiated. After 10 months of treatment, the ulcer completely healed and no adverse effects were experienced by the patient.

Severe forefoot infection complicated by Fusobacterium russii.

We present the first case of a complicated foot infection caused by Fusobacterium russii in Austria. F. russii is highly associated with mammals such as cats and dogs. Our case underlines the difficulties in isolation and identification of anaerobes and the pitfalls in antimicrobial treatment of polymicrobial infections.

[Cutaneous diphtheria after a minor injury in Sri Lanka]. / Kutane Diphtherie nach Bagatellverletzung in Sri Lanka.

Cutaneous dipththeria is an infectious bacterial disease endemic in tropical regions, but rarely diagnosed in Germany. Following travel in Sri Lanka, a 60-year-old German presented to our dermatological clinic with a skin ulcer and extensive erythematous erosive edema of his left foot. Corynebacterium diphtheriae was isolated from a swab of the lesion. There were no clinical signs of toxic diphtheria. The patient was treated with penicillin G and erythromycin, followed by a slow healing of the lesion. The isolated strain could be identified as toxigenic C. diphtheriae mitis. Due to increased travel activity, dermatologists should have uncommon infections like cutaneous diphtheria in mind.

Neuropathic ulcers in leprosy treated with intralesional platelet-rich plasma.

Neuropathic ulcers in leprosy represent a therapeutic challenge for clinicians. Chronic ulcers affect patient health, emotional state and quality of life, causing considerable morbidity and mortality in addition to contributing to significant health care costs. The pathogenesis is mainly related to the abnormally increased pressure in areas such as the sole of the foot, secondary to lack of sensation and deformities induced by peripheral sensory-motor neuropathy. Conventional treatment of these wounds can be slow due to their chronic inflammatory state and the senescence of local reparative cells. Platelet-rich plasma (PRP) may restore the healing process, leading to a reparative phase. We present two patients with four neuropathic leprosy ulcers that have responded satisfactory to PRP treatment. PRP therapy has been growing as a viable treatment alternative for chronic ulcers. However, stronger scientific evidence is required to support its potential benefit for use in chronic wounds.

Ozone therapy effectiveness in patients with ulcerous lesions due to diabetes mellitus.

INTRODUCTION: Development of purulo-necrotic foot lesions is one of the most dangerous surgical complications of diabetes mellitus, it causes high lethality, early disability, considerable economical expenses on treatment and rehabilitation. Mentioned above determine substantial actuality of diabetic foot problem and condition the necessity of further search of new ways and effective methods of lower extremities lesions complex treatment. THE AIM: of our research was to study the effectiveness of ozone use in complex therapy among patients with diabetic foot. MATERIAL AND METHODS: Under our observation were 47 patients with I and II stages of diabetic foot that correspond to superficial and deep ulcers without involving of subcutaneous tissue, ligaments, tendons and muscles into the process, without bone lesion, phlegmons and abscess forming according to Meggit-Wagner (1978) classification. Depending on treatment every group of patients was divided into subgroups. B group composed patients that received traditional therapy.A group composed patients that along with traditional therapy course received course of systemic and regional ozone therapy for 12-14 days, one session per day. Cytological examination of discharge from wounds was carried, lipid peroxidation state and antioxidant protection state was assessed. RESULTS: Ozone use has more evident clinical effect, significantly affects the phase course of wound process, promotes the improvement of lipid peroxidation and antioxidant protection indexes, reduces the length of hospital stay and term of treatment of patients with diabetic foot. СONCLUSIONS: Studies conducted showed that including of ozone therapy into complex surgical treatment has positive effect on wound process.

Community acquired multi drug resistant Staphylococcus aureus in a rural setting of North Western Ethiopia: a tough challenge.

Commnunity acquired Methicillin Resistant Staphylococcus aureus species are common causes of skin and soft tissue infections. Foot ulcer of former leprosy patients can be invaded by a multi-microbial infection. Cervicitis is usually caused by certain sexually transmitted agents. Here we report a series of cases of methicillin-resistant Staphylococcus aureus, isolated from two patients presenting with foot ulcer and cervicitis respectively, both in an outpatient or community setting (community onset) in rural North Western Ethiopia. The strains were resistant to all commonly available drugs such as trimethoprim-sulfamethoxazole, ciprofloxacin, erythromycin, chloramphenicol and tetracycline but sensitive to clindamycin. This is the first report of CA-MRSA in the study area.

[Paradoxical reactions and responses during antibiotic treatment for Mycobacterium ulcerans infection (Buruli ulcer). Four cases from French Guiana]. / Réponses et réactions paradoxales au cours du traitement médicamenteux de l'infection à Mycobacterium ulcerans (ulcère de Buruli). Quatre observations en Guyane française.

BACKGROUND: In recent years, first-line therapy for Mycobacterium ulcerans infection in French Guiana has consisted of antibiotics active against this organism. Two regimens are used comprising rifampicin associated with clarithromycin or amikacin. PATIENTS AND METHODS: We describe four patients presenting apparent worsening of their lesions during treatment: ulceration of a nodular lesion in a 32-year-old woman and worsening of an ulcerated lesion in three patients aged 16, 27 and 79 years. DISCUSSION: In these 4 patients, we concluded that the symptoms were caused by a paradoxical response or a reaction, a phenomenon already described in tuberculosis and leprosy. Such worsening is transient and must not be misinterpreted as failure to respond to treatment. The most plausible pathophysiological hypothesis involves the re-emergence of potentially necrotizing cellular immunity secondary to the loss of mycolactone, a necrotizing and immunosuppressive toxin produced by M. ulcerans, resulting from the action of the antibiotics.

Healing of leprosy-associated chronic plantar wounds with a novel biomembrane containing latex proteins from Calotropis procera.

Pre-clinical assays demonstrated that a 1% polyvinyl alcohol biomembrane containing latex proteins (10%) from the medicinal plant Calotropis procera was biocompatible and stimulated healing of incisional and excisional wounds in murine models, and the mechanistic aspects were established. The efficacy of the biomembrane (BioMemCpLP) to promote healing of chronic ulcers in leprosy patients was investigated. The study started with 28 volunteers. Five were excluded later due to different disconformities. Ulcers from 15 patients were continuously treated with BioMemCpLP for 56 days. Five patients were treated only with silver sulfadiazine and three patients received plain hydrocolloid wound dressings with high absorption capacity. In all cases, wound dressings were renewed three times a week for 56 days and ulcers were evaluated weekly for contraction and healing progress. The extent of the healed area in the ulcers treated with BioMemCpLP was greater than in the control groups. Approximately 88% of ulcers treated with BioMemCpLP were fully healed before day 56, against 6% in both control groups. This result was not correlated with age/gender, duration or location of ulcers, deformity or whether or not the patient was cured of leprosy. The results showed that BioMemCpLP was beneficial for treatment of ulcers suffered by leprosy patients without noticeable side effects.

Effects of bosentan on nondigital ulcers in patients with systemic sclerosis.

BACKGROUND: Bosentan is an oral dual endothelin receptor antagonist, which has been shown to be efficacious for preventing new digital ulcers in patients with systemic sclerosis (SSc) in two high-quality randomized controlled trials. However, its efficacy for nondigital ulcers in SSc remains unknown. OBJECTIVES: To evaluate the efficacy of bosentan on nondigital ulcers in patients with SSc. METHODS: Bosentan was administered to five patients with SSc with pulmonary arterial hypertension, who also had nondigital ulcers refractory to conventional treatments. The efficacy of bosentan on nondigital ulcers and its association with clinical features of ulcers were analysed. RESULTS: The nondigital ulcers refractory to conventional treatments were significantly improved by the administration of bosentan in cases surrounded with severe cyanosis. In contrast, nondigital ulcers without cyanosis were still refractory to bosentan therapy. CONCLUSIONS: Bosentan may be efficacious for accelerating the healing of nondigital ulcers with severe cyanosis, suggesting that nondigital ulcers caused by severely impaired peripheral circulation are highly responsive to this treatment.

Clinical antimicrobial photodynamic therapy: phase II studies in chronic wounds.

Microbiologically based diseases continue to pose serious global health problems. Effective alternative treatments that are not susceptible to resistance are sorely needed, and the killing of photosensitized bacteria through photodynamic therapy (PDT) may ultimately emerge as such an option. In preclinical research and early in vivo studies, PDT has demonstrated the ability to kill an assortment of microorganisms. Antimicrobial PDT has the potential to accelerate wound healing and prevent clinical infection, particularly in patients with chronic leg ulcers. Larger trials are needed to confirm its early promise and suggest its ultimate role in caring for chronic wounds.