High-Intensity, Low-Frequency Pulsed Electromagnetic Field as an Odd Treatment in a Patient with Mixed Foot Ulcer: A Case Report

In this case report, we documented the first add-on use of diamagnetic therapy in the treatment of foot mixed ulcer in an older woman. A mixed wound represents a challenge for clinicians, since there is still no optimal treatment algorithm [18]. Moreover, clinical management of older patients is further complicated by both comorbidity and polytherapy, which may reduce adherence to treatments and may increase the risk of drug interactions and adverse drug reactions [19,20]. Considering these factors, our patient was treated for 1 year with local treatments without a clinical improvement. After this period, she came to our observation, where medical doctors specializing in clinical pharmacology and vascular surgery suggested a combined treatment. Previous papers documented that patients with mixed ulcers should be managed with traditional methods or novel biologic dressings [5,18]. Compression therapy increases venous flow and lymphatic drainage and enhances fibrinolysis, improving the healing of ulcers and reducing ulcer recurrence rates [21]. However, it can only be performed in patients with ABI > 0.5 and an absolute ankle pressure >60 mmHg [22]. Other adjuvant therapy, such as hyperbaric oxygen therapy, showed benefits in short-term studies but reduced availability and costs limit its use [23].

In our patient, the vascular surgery excluded the possibility of surgery; therefore, a pharmacological treatment with the diamagnetic therapy was started with a rapid improvement in both pain and foot ulcer.

Magnetic fields, which are effective in pain relief, may have possible applications in chronic wounds, since they seem to affect all of the components in the healing process (e.g., fibrin, platelets, fibroblasts, and growth factors) [9,24]. Diamagnetism is a weak magnetic property of matter and its expression requires high MF values to exploit the diamagnetic properties of biological tissues, as with other forms of electromagnetic stimulation [25]. In this case report, the diamagnetic effect was exerted through HI-LF PEMF.

Several mechanisms have been proposed to explain why the PEMF may reduce the wound healing time. Preclinical data show that PEMF could stimulate vasodilatation, increasing the cutaneous capillaries’ blood flow and organ perfusion, reducing soft tissue edema, and increasing the metabolic activity [26,27]. Improved blood perfusion in the magnetically stimulated tissue is a mechanism for stimulatory effects in regenerative process, resulting in both accelerated cell proliferation and inhibition of the inflammation [28]. Lee et al. [29] reported that electricity and magnetic fields can modulate both reparative cell migration and ion channel activity in the wound area, and ion channel activity is involved in wound healing. We considered treatment with magnetic fields useful to accelerate recover only in the absence of a physiological electric current or biological activity in the restoration process.

The electrical signals generated by PEMF may act on injured cell membranes generating a reduction in inflammation, increases in fibroblasts and macrophages in the ulcer, and an increased deposition of fibrin [30]. Markoll et al. evidenced a decrease in matrix metalloproteases (MMPs) and an increase in the tissue inhibitor of MMPs (TIMP) mediated by pulsed magnetic fields [31]. These components play roles in ulcer pathogenesis and remodeling [32]. PEMF may also elicit their action, reducing the production of reactive oxygen species (ROS) [33,34].

Several anecdotal data on the beneficial properties of electromagnetic therapy for skin wounds are available but are not conclusive. Pulsed magnetic fields accelerate wound healing in rats: Strauch et al. described an increase in wound tensile strength 21 days after wounding [35]. Electromagnetic fields showed a certain effect in the modulation of scapular wounds artificially made on animals: the application without frequency modulation was effective in diminishing inflammatory exudation [36].

In a previous double-blind study, Ieran et al. [37] evaluated in 20 patients the effect of an electromagnetic field on the healing of venous ulcers, documenting that, with respect to the placebo, an electromagnetic field is able to improve the clinical symptoms, lowering the rate of ulcer recurrence (p < 0.02).

In agreement with this, in a prospective, randomized, double-blind, placebo-controlled study, Stiller et al. [38] evaluated the effect of pulsed electromagnetic limb ulcer therapy (PELUT) in the healing of recalcitrant, venous leg ulcers and showed that PELUT induced significant decreases in wound depth (p < 0.04) and pain intensity (p < 0.04) with respect to a placebo-treated group. Kenkre et al. recruited nineteen patients and used different frequency (600 Hz and 800 Hz) irradiations compared with a placebo. Patients treated with PEMF showed improvement in pain control and ulcer size, 800 Hz therapy seemed to be more effective than 600 Hz or placebo, and 68% of patients experienced adverse events: headache (treatment group only), sensation of heat, pins, and tingling (placebo and treatment groups) [39].

A lack of standardization of PEMF devices in terms of type, duration, frequency, and intensity and length of exposure is a relevant issue [30]. Gordon described an increase in time (dB/dt) as a critical determinant of efficacy in this kind of treatment, performing a major effect in the activation of restoration genes [33]. Magnetic field therapy should be provided in doses similar to a drug [9]; therefore, physicians should develop the ability to tailor the right protocol for patients’ pathology and characteristics. Despite the presence of vascular effects supporting their use [9,26,27,29], there were no data on patients suffering from arterial ulcers treated with PEMF. In a mixed etiology leg ulcer, a combined 9-week treatment including hyperbaric oxygen, an extremely low-frequency variable magnetic field, and low-energy light radiation resulted in complete healing and subsequent pain relief [40]. Magnetic fields seem to have promising application prospects also in diabetic wound healing, notwithstanding the lack of general agreement on the mechanisms underlying its biological and therapeutic effects [41].

Although the literature documents a lack of high-quality evidence regarding PEMF in ulcer management [30], we observed the complete healing of a mixed ulcer from which a patient suffered for a year at the ninth week of a combined protocol without the development of adverse events. However, the impact of the global care process should be considered, since the interventions carried out during the entire treatment period cannot be separately assessed.

Indeed, being a single case, we cannot exclude that other factors could have a role in the management of venous ulcer, e.g., the quality of debridement and compression and the discontinuation of steroid therapy.

In the future, advanced visualization of magnetic fields and the presence of physicists in the medical team may be useful in deeply understanding the interaction of waves with the organism and in achieving a more specific administration [42]. Indeed, it would be of interest evaluate the possibility of using magnetophoresis (i.e., the enhancement of drug permeation across the biological barriers through a magnetic field) to deliver topical drugs in addition to magnetic fields in wound treatment. This process may exert an enforcing action in the treatment of ulcer. Magnetophoresis has been shown to increase the dermal bioavailability of certain drugs, potentially enhancing delivery and pharmacological effects [43,44]. However, to our knowledge, there are no known add-on drugs used in diamagnetic therapy in the management of ulcers. Furthermore, whether magnetic fields may exert other effects on drugs pharmacokinetics and pharmacodynamics should be considered.

In conclusion, our case report suggests that diamagnetic therapy might represent an interesting noninvasive option as an add-on treatment for patients with venous ulcers. Preclinical data describe several mechanisms through which it might accelerate healing processes and promote drainage, whereas clinical data are limited to anecdotal reports and small clinical studies. Larger randomized control trials and standardized diagnostical and therapeutical procedures are needed to compare the results and to obtain high-quality evidence. Furthermore, the interactions between magnetic fields and add-on drugs need further analysis.