Successful wound healing of refractory digital ulcer in patient with systemic sclerosis by Waon therapy

Abstract

The treatment of digital ulcer (DU) in systemic sclerosis (SSc) has not been established. A 77-year-old female with a refractory DU in SSc on the right foot was transferred to our hospital. Wound healing had not been achieved despite several endovascular treatments (EVT) and minor amputations. We started Waon therapy 5 days per week as an adjunct therapy. She was placed in a far-infrared-ray dry sauna maintained at 45 °C for 15 min, and was subsequently kept to rest with soothing warmth using a blanket for additional 30 min outside the room. Gradually, the wound had become smaller and the skin perfusion pressure (SPP) had increased. The increase of the blood flow to the wound could be observed in the angiogram on day 109. An additional EVT on day 109 also accelerated wound healing. Finally, wound healing was completely achieved without additional amputations on day 173. In this presented case, Waon therapy contributed to increase of the blood flow to the wound, evidenced by SPP value. Waon therapy may serve as an effective adjunct therapy of DU in SSc.

<Learning objective: Digital ulcer (DU) frequently occurs in patients with systemic sclerosis (SSc). However, the treatment of them has not been established. We experienced a case of complete wound healing of DU in SSc following Waon therapy. Waon therapy has a potential to increase the microcirculation, as evidenced by increased SPP and angiogram. Waon therapy can be considered one option of adjunct therapy for the patient with refractory DU in SSc.>

Introduction

Systemic sclerosis (SSc) is a multi-organ disease characterized by wide-spread fibrosis, activation of immune cells, production of autoantibodies and extensive damage of the micro-vessels [1]. Patients with SSc frequently experience digital ulcer (DU) because of inadequate peripheral blood supply [2]. DU has been related to tissue ischemia from several processes, including vasospasm secondary to Raynaud's phenomenon or intimal fibro-proliferation [1]. DU occurs in 30–58% of the SSc patients, and not a few patients with SSc require limb amputation [2]. Nonetheless, successful management of DU in SSc has not been adequately reported [3].

Waon therapy is a form of thermal therapy, namely soothing warm therapy, which differs from the traditional sauna with a high temperature [4]. It has been demonstrated effective for chronic limb-threatening ischemia (CLTI) as well as for severe cardiac failure [5]. It is performed as follows: a patient is warmed in an evenly heated dry-sauna room at 40–60 °C for 15 min. The patient is kept on a bed to rest with soothing warmth using a blanket for additional 30 min outside the chamber, and is supplied fluids to replace the loss from perspiration. The deep-body temperature rises approximately 1.0–1.2 °C. Waon therapy can increase blood flow by vasodilation, angiogenesis and improvement of vascular endothelial function [5].

We herein report a patient with DU in SSc who achieved complete wound healing of DU following Waon therapy.

Case report

A 77-year-old female was transferred to our hospital for the treatment of a refractory DU on the right foot. She was diagnosed with limited cutaneous SSc two years earlier, comprising digital ulcer, skin tightening, sausage appearance of the fingers and anti-centromere antibodies. She had complained of a severe pain, and the digital ulcers were observed from the first to third toes and the fifth toe on the right foot since a year before the transfer. Endovascular treatment (EVT) had been performed 3 times in 8 months for the repeated occlusions of the anterior tibial artery (ATA) and the posterior tibial artery (PTA). Besides, toe amputations and additional Lisfranc's amputation had been performed stepwisely. However, wound healing had not been achieved.

On admission to our hospital, necrotic tissue was seen on the amputated surface of the wound. The overall picture of the right foot is shown in Fig. 1a. The laboratory data was as follows: white cell count, 5.7 × 10³/µL; hemoglobin, 13.8 g/dL; albumin, 4.3 g/dL; CRP, 0.08 mg/dL. Although her ankle brachial index was 1.44 on the right and 1.22 on the left, skin perfusion pressure (SPP) showed insufficient values of 30 mmHg in the dorsal side and 38 mmHg in the plantar side. SPP in the dorsal side was measured on a few centimeters proximal from the wound, showing cross mark in Fig. 1a. Amlodipine (5 mg, daily), isosorbide mononitrate (20 mg), aspirin (100 mg), clopidogrel (75 mg) were prescribed, but she had not received any specific medical treatments for SSc such as prostacyclin analogues, endothelin receptor antagonists or low-dose steroids.

Fig. 1.

Time course of the wound

(a) The overall picture of the right foot on admission is shown. The necrotic tissue was seen on the surface of the wound.

(b) Waon therapy was started on day 5. The margin of the wound looked clearer on day 43. Skin perfusion pressure (SPP) value gradually increased. We applied the vacuum-assisted wound closure. However, it could not be continued because of infection.

(c) The reduction of the necrotic tissue can be seen. Waon therapy was continued, and the SPP had increased.

(d) On day 109, endovascular treatment (EVT) was performed for the re-occlusion of below-the-knee artery, resulting in achievement of peak SPP value. On day 121, the favorable granulation can be seen, and the range of the wound became smaller.

(e) Although the SPP value reduced gradually, wound healing was advanced.

(f) Wound healing was completely achieved.

For her limb salvage, we started Waon therapy as an adjunct therapy from day 5. A far-infrared-ray dry sauna room was set at 45 °C, and Waon therapy was performed 5 days per week. On day 43, a margin of the wound became clearer [Fig. 1b]. Besides, SPP on day 44 increased to 50 mmHg in the dorsal side and 54 mmHg in the plantar side [Fig.2]. We performed debridement and applied the vacuum-assisted wound closure (VAC) to accelerated wound healing. However, methicillin-resistant staphylococcus aureus (MRSA) was detected from the wound on day 61, and VAC application was suspended. Cleansing of the wound, applying a topical ointment and administrating an intravenous antibiotic therapy (vancomycin) were conducted for a month, resulting in eradication of MRSA. Waon therapy was continued during the treatment of MRSA because there was no systemic inflammation, and the reduction of the necrotic tissue can be seen with increased SPP value [Fig.1c]. On day 109, we performed EVT to treat the re-occlusions of the right ATA and PTA by balloon angioplasty for acceleration of the complete would healing [Fig.3a, 3b]. On the initial angiogram, it seemed that blood flow to the wound was increased compared to the angiogram before Waon therapy [Fig.3c, 3d]. The angiogram after EVT showed the best blood flow [Fig.3e]. These angiographies were performed by manual injection with 5 ml contrast added a little of normal saline, and the catheter was placed at popliteal artery. They were performed with almost similar condition. After all, SPP increased to 70 mmHg in the dorsal side and 85 mmHg in the plantar side on day 123. Favorable granulation appeared and the wound became smaller [Fig.1d, 1e]. Although SPP decreased due to the re-occlusions of the tibial arteries, we finally achieved complete wound healing without any amputations [Fig.1f]. Waon therapy was finished on day 173 and she was discharged on day 179. At 12-month follow-up, digital ulcer did not recur without Waon therapy.

Fig. 2.

Time course of skin perfusion pressure

The figure shows the changes of the SPP value after Waon therapy started. The SPP value gradually increased. On day 109, EVT was performed and the SPP achieved to the peak value. After that, SPP decreased due to the re-occlusions of the tibial arteries.

Fig. 3.

Time course of angiogram

(a) This is a pretreatment angiogram in below the knee artery. White arrows show anterior tibial artery (ATA) and posterior tibial artery (PTA). Both arteries are occluded.

(b) This is a final angiogram in below the knee artery. Both ATA and PTA are successfully revascularized.

(c) This is a pretreatment angiogram in below the ankle artery before Waon therapy.

(d) This is a pretreatment angiogram in below the ankle artery after Waon therapy (On day 109). It seemed that blood flow to the wound increased compared to the angiogram before Waon therapy.

(e) This is a final angiogram after EVT for the right ATA and PTA on day 109. The blood flow to the wound was increased markedly.

Discussion

We experienced complete wound healing of DU in SSc following Waon therapy. Since Waon therapy started, SPP had increased from 30 mmHg to 74 mmHg in the dorsal side and 38 mmHg to 60 mmHg in the plantar side. Although EVT on day 109 might accelerate wound healing, Waon therapy enhanced wound healing through improving the microcirculation, as evidenced by increased SPP and angiogram.

DU in SSc is often refractory. The European League against Rheumatism (EULAR) recommends intravenous (IV) iloprost, PDE-5 inhibitors and bosentan as pharmacotherapies for DU in SSc. However, many patients with SSc are resistant to these medical treatments. Besides, outcomes after revascularization by EVT in CLTI patients with collagen diseases remain poor [6]. DU in SSc is particularly refractory because SSc-related vasculopathy is primarily due to the microvascular disorder with the coexisting macrovascular disorder [7]. Approaches to both microvascular and macrovascular disorders are required for wound healing.

The pathogenesis of DU in SSc is considered as Raynaud's phenomenon and intimal fibro-proliferation [1]. Raynaud's phenomenon occurs due to vasospasm of digital arteries triggered by cold exposure or emotional stress. It shows the three characteristic phases of pallor, cyanosis, and erythema correlating with reduced blood flow, total loss of oxygen supply, and reperfusion [8]. Recurrent ischemia-reperfusion injury and the subsequent generation of reactive oxygen species lead to vascular and tissue damage. Intimal fibro-proliferation occurs due to autoimmune vasculopathy. The autoimmune state in SSc reduced suppressive function of regulatory T cells, leading to generation of excessive molecular mediators, cytokines and growth factors. They promote endothelial damage, resulting in intimal fibro-proliferation [9].

Waon therapy has a potential to increase microcirculation. First, it promotes peripheral vasodilation by relief of Raynaud's phenomenon. Second, it reduces oxidative stress and improves endothelial function through increase of endothelial nitric oxide production, leading to prevention of vascular remodeling [10]. Third, it is reported that new collateral vessels can be generated [5]. All these effects of Waon therapy could improve microcirculation.

EVT, the treatment for the macrovascular disorder, is also important for wound healing. However, its patency is limited especially in cases with poor microcirculation. EVT may be more effective when it is applied after improvement of microcirculation by Waon therapy.

Waon therapy is applicable for the patient with refractory digital ulcer by insufficient microcirculation such as DU in SSc or desert foot of CLTI characterized by occlusions of the foot arteries including the dorsal pedis, lateral tarsal artery, both plantar arteries, and the plantar arch. On the other hand, patients with active systemic infection, high fever, low blood pressure uncontrolled hypertension, severe aortic valve stenosis, hypertrophic obstructive cardiomyopathy and dehydration should be excluded to apply them. Waon therapy can be continued for the patients with local infection, which is defined as infection localized to the wound and not spread throughout the body. Our presented case demonstrated that proper wound care and administrating antibiotics can prevent the expansion of infection in localized infectious wound, even if Waon therapy is continued.

Conclusions

We could achieve complete wound healing of DU in SSc following Waon therapy. Waon therapy may serve as an effective adjunct therapy of DU in SSc.

Declaration of Competing Interest

The Authors declare that there is no conflict of interest.