Efficacy and long-term longitudinal follow-up of bone marrow mesenchymal cell transplantation therapy in a diabetic patient with recurrent lower limb bullosis diabeticorum

Abstract

Bullosis diabeticorum is a rare presentation of cutaneous manifestation most commonly affecting the lower limbs in patients with diabetes. The appearance, often as insidious as its resolution, is characterized by tense blisters on the skin surfaces of the lower limbs and the feet. The cause still remains unclear, but it may relate to microangiopathy and neuropathy. In this report, we present a case of a 64-year-old male with multiple episodes of blistering in the left lateral lower limb after a traumatic fall who was subsequently diagnosed with type 2 diabetes mellitus. The patient had a history of poorly controlled blood glucose and subsequently developed vasculopathy and peripheral neuropathy. Despite appropriate glycemic control and antibiotics therapy, the patient developed recurrent bullosis diabeticorum on five separate occasions during a 2-year span from 2005 to 2007. Building on our success with ischemic diabetic foot, we used bone marrow mesenchymal stem cell (BMMSC) transplantation therapy for bullosis diabeticorum. After a 9-month treatment, this patient developed another episode of cellulitis in the same lower limb which was successfully treated with antibacterial therapy. It is interesting that the patient reported no recurrence in the next 10-year follow-up span. This study demonstrates that bullosis diabeticorum could appear even before the onset of diabetes, and vascular insufficiency predisposes to the occurrence of bullosis diabeticorum. Our findings suggest that autologous BMMSC transplantation therapy may be an effective measure for recurrent bullosis diabeticorum; however, this will require further investigation to be conclusive. Early identification of diabetes and its complications and appropriate treatment may improve clinical outcomes and prevent lower limb amputation.

Trial registration: ClinicalTrials.gov Identifier: NCT00955669 . Registered on August 10, 2009.

Keywords: Bone marrow mesenchymal stem cells; Bullosis diabeticorum; Diabetes mellitus; Diabetic peripheral arterial disease.

Conflict of interest statement

Ethics approval and consent to participate

This clinical study was approved by the ethical committee board of Southwest Hospital. The patient provided written informed consent prior to participation in this study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

a Bullosis diabeticorum with skin ulcer. b Bullosis diabticorum with diabetic osteomyelitis. c Bullosis diabeticorum with wet gangrene

Fig. 2

a-d Ischemic bullosis diabeticorum. e-h Neuropathic bullosis diabeticorum

Fig. 3

Bone marrow mesenchymal stem cell (BMMSC) transplantation procedure. a Extraction of bone marrow under disinfected and anesthetic conditions. b The mononuclear stem cell layer was harvested with density gradient centrifugation. c BMMSC morphology after 21 days of culture. d Subcutaneous cellulitis with bullosis diabeticorum. e Administration of BMMSCs with normal saline. f The left lower limb 10 years after BMMSC treatment