A case of dominant dystrophic epidermolysis bullosa with diabetes mellitus presenting as progressive recalcitrant blisters and erosions (2013)

Dominant dystrophic epidermolysis bullosa (DDEB) is a rare inherited blistering disorder resulting from mutations in the COL7A1 gene. This gene encodes type VII collagen, a major component of anchoring fibrils, at the dermal–epidermal junction. Its clinical features include recurrent blisters that primarily occur on the extremities as well as nail dystrophy. Here, we report a case of DDEB presenting as recent progressive recalcitrant blisters, which may be related to the onset of diabetes mellitus. A 71-year-old man was referred to our hospital with recent progressive recalcitrant blisters and erosions. The patient had been suffering from recurrent trauma-induced skin blisters and erosions on the dorsal aspects of the legs and arms since birth. The skin lesions healed within one month with only mild scarring; therefore, he had not received special medical treatment for the clinical manifestations. However, the patient reported that the erosions and blisters had gradually become recalcitrant over the past year so he decided to visit the department of dermatology. On examination, the patient presented with blisters and erosions that had healed with mild scarring and milia on the legs and elbows (Figure 1A, B) as well as nail dystrophy (Figure 1C). Sensory perception on the extremities was intact. His great-grandmother, grandfather, father and daughter suffered from similar skin symptoms. A skin biopsy from a blister on his knee showed subepidermal bulla formation, mild perivascular lymphoid infiltration and hyalinizing fibrosis (Figure 1D). The epidermal basal layer was disarranged. Electron microscopy showed a lack of anchoring fibrils at the base of the bulla (Figure 1E). On the basis of these findings, the patient was given a clinical diagnosis of DDEB. To confirm the diagnosis of DDEB by mutational analysis, DNA extraction from a peripheral blood sample was performed. The COL7A1 gene was scanned with polymerase chain reaction amplification and heteroduplex analysis. Direct nucleotide sequencing of genomic DNA and restriction fragment length polymorphism showed that the patient was heterozygous for 17 nucleotide deletions and 2 insertions in exon 109 of the COL7A1, which was consistent with DDEB. Laboratory data showed a haemoglobin A1c level of 11.8% and a casual blood glucose level of 322 mg/dl. His blood glucose level one year before this visit was within normal range. After controlling his diabetes mellitus with insulin therapy, recalcitrant erosions and blisters became much milder than before. This case of DDEB presented as progressive recalcitrant blisters and erosions in accordance with the onset of diabetes mellitus. The incidence of intractable wounds in association with diabetes mellitus has increased as a result of the increase in the elderly population, especially in developed countries 1. Impaired wound healing in diabetes mellitus is usually a result of macro- and micro-angiopathy as well as neuropathy 2. Ischaemia impairs wound healing by delaying or preventing the flow of oxygen, nutrients, antibiotics and the components required for healing 3. One study reported that a long duration of diabetes mellitus and poor glycaemic control are risk factors for the development of foot ulcers in patients with diabetes mellitus 3. In our case, we were unable to accurately determine the duration of diabetes mellitus, but the possibility exists that the onset of diabetes mellitus resulted in the skin lesions being recalcitrant. Intriguingly, the recalcitrant erosions and blisters became milder after controlling diabetes mellitus. Our case suggests that clinicians should observe the wounds of patients with DDEB carefully, taking into consideration that the wound healing process may be affected by other systemic diseases, such as diabetes mellitus. Kio Park1, Hajime Nakano2, Daisuke Sawamura2, Kenji Kabashima3 & Yoshiki Miyachi3 1Department of Dermatology, Yamato Takada Municipal Hospital, Nara, Japan kiopark2@gmail.com 2Department of Dermatology, Hirosaki University, Aomori, Japan 3Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan