Treatment of diabetic foot ulcer with medicinal leech therapy and honey curcumin dressing:a case report

Shirbeigi Laila,Eghbalian Fatemeh,Bakhtyari Lida＊

1Department of Iranian Traditional Medicine,School of Traditional Medicine,Tehran University of Medical Sciences,Tehran 1668753961,Iran.2Research Institute for Islamic and Complementary Medicine,School of Persian Medicine,Iran University of Medical Sciences,Tehran 1449614535,Iran.

Abstract

Keywords:Hirudotherapy,Leech therapy,Diabetic foot ulcer,Gangrene,Diabetic foot wound,Medicinal leech

Background

Diabetic foot ulcers(DFUs)is a complication of uncontrolled diabetes.In the long term,hyperglycemia results in peripheral vascular disease and neuropathy and could require amputation of the limb.Frequent trauma and constant pressure make the plantar region more susceptible to wounds.The treatment requires a multilateral approach[1].One case of amputation due to diabetes occurs every 30 minutes in the world.The mortality rate of DFUs is ranked the highest after cancer[2].The treatments for DFUs in conventional medicine include debridement of the ulcer,infection management,revascularization,hyperbaric oxygen therapy,and negative-pressurewound therapy,if needed.However,evidence of their efficacy and cost-effectiveness is limited[1,3].Favorable results have been obtained from leech therapy in therapeutic protocols,such as transplantation surgery,diseases,such aschronic ulcers,varicose vein,phlebitis,thrombotic conditions,asthma,hypertension,migraines,and different types of pain,such as sciatica and osteoarthritis[4].Leech therapy was traditionally used for various ailments,but nowadays,its role has been limited to relieving venouscongestion in microsurgeries.The oldest documentation of leech therapy is a painting in an Egyptian tomb from 1500 B.C.E.In Europe,the most wide-spread therapeutic use of leeches occurred in the 17th and 18th century,whilein the Arab countries,itwaslimited to bloodletting.During the early 20th century C.E.,and at the time of introduction of the germ theory,leech therapy was overlooked.In the 21st century,studies were conducted on the utility of leeches in ailments such as arthritis [5].The Food and Drug Administration legalized medicinal leech therapy in June 2004.In Iranian traditional medicine(ITM),disease treatments have three components:lifestyle modification,medicinal herbs,and manual interventions.Leech therapy is a widely used manual intervention in ITM,especially for chronic sores[6].In leech therapy,blood is sucked from a deeper source compared to wet cupping[7].Seyyed Esmaeel Jorjan,an Iranian scholar from the 12th century,in the book titled Zakhiree-Kharazmshahi,mentioned the benefits of leech therapy in chronic ulcers and skin diseases[8].Additionally,in the book titled Canon of Medicine,Avicenna described the medicinal leech’s appearance and specifications and differentiated them from other species[7].This method is still in used by ITM specialists.A complication of leech therapy is bacterial infections,which can be prevented by prophylactic antibiotics against the most common transmissible pathogens from leeches to humans [9].A sub-therapeutic dosage of antibiotics can be used to decrease the antibiotic resistance rate [10].Furthermore,natural honey and curcumin can prevent wound infection and edema and remove dead tissues surrounding the wound[11].In the present study,diabetic foot ulcer(DFU)was successfully treated with ITM.

Table1 Wagner classification

Case Report

Chief complaint and presenting illness

The patient was a 77-year-old man with the chief complaint of painful wound in the foot.There was a 2.5×2.0 cm painful wound on the right first toe,that formed two months previously,according to the patient.Based on Wagner's classification of DFUs(Table1),the wound was of grade 2(deep wound with muscle involvement)[12].The pain was of grade 8 on the visual analogue scale(VAS),and tenderness was detected.There was no fever.The other findings were cold foot,dry and shiny skin,decrease in limb hair,absence of the dorsalis pedis arterial pulse,and absent tactile sensation.

Physical examination:the patient was alert,with BP:120/80 mmHg,heart rate:110/min,respiratory rate:16/min,decreased visual acuity and partial hearing loss due to senile.There was no chest pain or respiratory symptoms.The abdomen was soft and non-tender.The upper extremities had no abnormalities,while the lower extremity was cold,shiny,and hairless.The left foot had been amputated in the metatarsal region,and the dorsalis pedis arterial pulse was absent.

Laboratory tests:Fasting blood sugar:98 mg/dL(normal range:70-99 mg/dL),2 hours postprandial blood sugar:120 mg/dL(normal range:＜145mg/dL),Hb A1C:5.3 g/dL(normal range:＜5.7%),and other test items were shown in Table2.

Past medical history and drugs

The patient had a history of diabetes mellitus type 2 for 30 years and had been on insulin for 15 years(present dose:insulin regular,8 U;NPH insulin,27 U).Further,he was on 100 mg of celecoxib daily for relief of pain in the foot due to DFU.The first toe and the middle toe of left foot were amputated at the age of 55 years because of microvascular complications from gangrene,and six months afterwards,the other three toes were amputated for the same reason.After amputation,percutaneous transluminal angioplasty was performed to remove femoropopliteal arterial occlusion.However,because of the spread of infection,the metatarsal region was amputated additionally.He had hypertension for 20 years and had been on 50 mg of valsartan,20 mg of furosemide,10 mg of amlodipine,and 20 mg of citalopram daily to manage paresthesia in the feet and hands.The patienthad undergone coronary artery bypass grafting at the age of 54 years and had been taking 100 mg of acetyl salicylic acid(ASA)daily since that.He had undergone retinal laser surgery in his 50 years.Moreover,he had cerebrovascular accident at the age of 69 years.

Table2 Laboratory tests

Treatment

Treatment process

The patient was treated at the Ahmadieh Clinic(Iranian Medicine Clinic of Tehran University of Medical Sciences)with two medium-size leeches in one step.The foot was washed with warm water and dried.Subsequently,leeches were manually placed near the wound.The leeches did not bite at first;therefore,the skin was scratched with a needle.Subsequently,the leech bit and sucked blood for 30 minutes and left the skin.Finally,the wound was covered with topical honey and curcumin(Figure1 A).The patient was prescribed with 500 mg of oral ciprofloxacin twice daily for 10 days.None of the patient’s ongoing medications were altered.

Therapeutic effects

After the leech therapy,pain was evaluated on VAS,and DFU was graded based on Wagner’s classification system.Immediately after the leech therapy,pain increased to a VAS score of 9-10.After 2 days,pain decreased to a VAS score of 6,and at the end of the 2ndday,the pain completely disappeared.The wound was remarkably healed in 3 weeks(Wagner’s grade 1).There were no traces of the wound after 12 weeks(Figure1 B,C,D,E).

Discussion

The pathophysiology of the DFUs and soft-tissue infection is due to peripheral arterial occlusion,neuropathy and trauma. Diabetic neuropathy results in foot deformity, leading to increased skin pressure when walking. During DFUs development, the risk of infection of the limb increase dramatically because of poor blood circulation and limb is chemia [13]. One of the most effective proceedings for healing DFUs appears to improve the proper blood flow that is impaired in diabetes.

Table3 lists some enzymatic properties of leech that reduce ischemia and infection.For example,the anticoagulant,inhibition of platelet function and increasing blood flow effects of leech enzymes could help to establish the proper blood flow.Also,their anti-inflammatory and antimicrobial effects would accelerate the process of wound healing and reduce the wound infection[9].These effects can be enhanced through extracellular matrix degeneration mediated by hyaluronidase and collagenase contained in leech,which increase the enzymatic effects on the affected tissues.In addition,this patient had been on ASA for a long time.However,this was a limitation of the study,as we do not know if the treatment outcome was influenced by ASA.We need further studies on the effect ofASA on the outcome of leech therapy.

Figure1 DFU before and after leech therapy

In 2014,Hassan Hajtalebi treated a cyanotic and severely infected DFU using leech therapy for 10 sessions in combination with oral herbal therapy,full back cupping,and modern blood sugar control drugs.The patient's DFU healed completely,and blood sugar was controlled[14].In another study,he treated grade-4 DFU using leech therapy for 16 sessions in combination with herbal therapy,full back cupping,massage therapy,and conventional anti-hyperglycemic drugs.In 60thdays,complete wound healing,improvement in physical and mental states,and blood sugar control were achieved[15].Compared to our case,the wounds in these two cases were higher in grade,and general illness was obvious.Further,our treatment was simpler,with only one session of leeching plus curcumin and natural honey dressing.However,we expectbetterefficacy and shorter treatmentduration with a combination ofthese methods.All of these methods were cost-effective and showed better outcomes compared to amputation.Furthermore,some studies showed that the leech's saliva had potential to reduce blood sugar levels.In a study by Mohammed AA in 2013,injection of leeches’salivary enzymes in diabetic rats regulated blood glucose[16].Arsheed Iqbal reported the efficacy of leech therapy for 3 months with constant intervals in a DFU patient.The ulcers were completely healed,without any recurrence,in one year of consistent follow-ups[17].In another study in 2017,Dr.Lalita Meena performed leech therapy for almost 3 months along with conservative management in a 45-year-old man with DFU and gangrene of 2 lateral toes.The ulcer healed completely,and the foot was saved[18].In India,Zaidi SM treated a grade-4 diabetic wound with leech therapy and oral herbal therapy,which regulated blood sugar and lipid profile and completely healed the wound[2].

Here,a dressing of natural honey and curcumin was used after the leech therapy.Honey is a common component of ITM for most types of the wound[19].According to Makhzan al Advieh,a drug book of ITM,natural honey and curcumin clear the pus and honey debrides the wound.Therefore,honey can be used to treat chronic,infective,and resistant ulcers.The antioxidants in honey can break the free radical chains that harm the injured area.Moreover,the anti-inflammatory,anti-microbial,and moisturizing effects of honey can promote angiogenesis and oxygen circulation,leading to wound healing[20].In February 2019,Wanget al.performed a systematic review of honey and diabetic wounds.The meta-analysis showed thathoney dressing efficiently decreased wound debridementand improved healing and bacterial clearance period in one to two weeks of use[21].Curcumin,the most active component of the rhizome ofCurcuma longa L.(common name:turmeric),has been studied for many years for its antioxidant,radical scavenger,antimicrobial,and anti-inflammatory effects,which play key roles in wound healing.Additionally,curcumin activates growth factor production,which is involved in wound healing,and accelerates wound repair[22].In May 2019,Fereidooniet al.performed a study on the effects of curcumin nanofibers on wound healing.The technique is called electrospinning and has the ability of sustained drug release and oxygen delivery to the wound through nanofibers,leading to wound healing [23].Although both honey and curcumin have antimicrobial and anti-inflammatory effects,they do not have the ability to cause blood dilution and recirculation in the affected area,which are crucial to treat DFUs.The limitation of this study was the lack of comparison of the curative effects between leech therapy combined with honey and curcumin and honey and curcumin dressing alone.Based on previous reports,500 mg of ciprofloxacin was prescribed after the leech therapy [24,25].Considering the efficacy,low cost,and minimal side effects,leech therapy appears to be a proper treatment for DFU.

Table3 Enzymes from medicinal leeches and their properties

Conclusion

Leech therapy in combination with honey and curcumin dressing is effective against disease progression in patients with DFUs.