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Dermatology > BULLOUS DISEASES
Bullous Disease of Diabetes
Article Last Updated: Jun 28, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Jacqueline M Junkins-Hopkins, MD, Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Jacqueline M Junkins-Hopkins is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and American Society of Dermatopathology
Editors: Maureen B Poh-Fitzpatrick, MD, Professor Emerita of Dermatology and Special Lecturer, Columbia University; Professor of Medicine (Dermatology), University of Tennessee; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
bullosis diabeticorum, diabetic bullae, diabetes mellitus, diabetic disease, type 1 diabetes, insulin-dependent diabetes, diabetes complications, uncomplicated diabetes, type 2 diabetes
Background
Bullosis diabeticorum is a distinct, spontaneous, noninflammatory, blistering condition of acral skin unique to patients with diabetes mellitus. Krane first reported this condition in 1930; Cantwell and Martz are credited with naming the condition in 1967. It is also termed bullous disease of diabetes and diabetic bullae.
Pathophysiology
The etiology of bullosis diabeticorum is not known. The role of trauma has been speculated; however, this alone does not explain the often spontaneous development of multiple lesions at several locations. The pathophysiology is likely multifactorial.
Many, but not all, patients with this condition have nephropathy or neuropathy; some authors have hypothesized an etiologic association, possibly related to a local, subbasement, membrane-zone, connective-tissue alteration. Hyalinosis of small vessels noted on biopsy specimens has led some authorities to speculate microangiopathy-associated blister induction.
Some electron microscopic evidence has suggested an abnormality in anchoring fibrils. A reduced threshold to suction-induced blister formation has been reported. Prominent acral accentuation of these lesions suggests a susceptibility to trauma-induced changes, but the definitive explanation awaits elucidation.
Frequency
United States
Bullosis diabeticorum tends to arise in patients with long-standing diabetes mellitus or with multiple complications of the disease. It has been reported to occur in approximately 0.5% of diabetic patients. Patients with uncomplicated or newly diagnosed disease, including type 2 diabetes, also may be affected.
Mortality/Morbidity
Blisters may recur; lesions tend to heal without significant scarring. No significant morbidity is associated with this condition unless secondary infection occurs. One report has described osteomyelitis arising at a site of bullosis diabeticorum.
Sex
A male-to-female ratio of 2:1 is reported in the literature.
Age
The reported age of onset ranges from 17-84 years.
History
- Blisters occur spontaneously and abruptly, often over night, and usually without known antecedent trauma.
- Lesions tend to be asymptomatic, although mild discomfort or burning has been described.
- Blisters heal spontaneously within 2-6 weeks of onset.
Physical
- Bullosis diabeticorum manifests as tense, nontender blisters arising on nonerythematous skin.
- Blisters typically occur on the feet or lower legs (see Media File 1), but they also may occur on fingers, toes, hands, and arms.
- Blisters tend to be large (from 0.5-17 cm in diameter), often with an irregular shape (see Media File 2), simulating a burn.
- Rarely, nonacral sites (eg, trunk) may be involved.
Causes
Prominent acral accentuation of these lesions suggests a susceptibility to trauma-induced changes, but the definitive explanation awaits elucidation.
Bullous Pemphigoid
Burns, Chemical
Burns, Electrical
Drug-Induced Bullous Disorders
Epidermolysis Bullosa
Epidermolysis Bullosa Acquisita
Friction Blisters
Porphyria Cutanea Tarda
Pseudoporphyria
Other Problems to be Considered
Blistering distal dactylitis
Lab Studies
- Consider evaluation of porphyrin levels if lesions prominently involve the hands. Elevated levels may indicate porphyria cutanea tarda. Levels reportedly are normal in persons with bullosis diabeticorum.
Other Tests
- Immunofluorescence: No primary immunologic abnormality is noted. Nonspecific capillary-associated immunoglobulin M and C3 has been reported rarely. Immunofluorescence findings have not been consistently reproduced by others, and direct immunofluorescence findings are usually negative. This study may be required to exclude clinically similar conditions (eg, bullous pemphigoid, epidermolysis bullosa acquisita) that typically show deposition of C3 and immunoglobulin G along the basement membrane zone.
Procedures
- Skin biopsy
- Consider shave biopsy or excisional/incisional biopsy to help distinguish bullosis diabeticorum from clinically similar conditions.
- For routine histologic sections, include the blister and portions of the underlying dermis in the biopsy, and submit it in formalin. For biopsy findings, see Histologic Findings.
- Histologic features of bullosis diabeticorum are not entirely specific; consider direct immunofluorescence studies to exclude histologically similar entities (eg, noninflammatory bullous pemphigoid, epidermolysis bullosa acquisita, porphyria cutanea tarda). Include perilesional uninvolved skin in biopsy for direct immunofluorescence and submit it in special transport medium (eg, Michel).
Histologic Findings
Lesions of bullosis diabeticorum have a heterogeneous histologic presentation. The blister plane may appear in a subcorneal, intraepidermal, or subepidermal location. Histology of fresh blisters tends to show an epidermal-dermal separation (see Media File 3). The variable blister plane likely is related to the blister age because reepithelialization can occur within days of blister onset. The blister cavity contains sterile proteinaceous fluid; an inflammatory component is absent or insignificant. Surrounding epidermis does not show significant change; however, rare reports describe associated spongiosis and degenerative keratinocytic pallor. Dermal changes (eg, capillary wall thickening, dermal sclerosis) may reflect the patient's underlying diabetes mellitus (see Media File 4). Caterpillar bodies typical of porphyria have been reported in lesions of bullosis diabeticorum. Electron microscopy of fresh blisters reveals separation in a subepidermal location, residing in the lamina lucida or the sublamina densa. Anchoring fibrils and hemidesmosomes are reported absent or decreased in early blisters.
Medical Care
Specific treatment is unnecessary because the condition is self-limiting.
Surgical Care
Secondary tissue necrosis may necessitate debridement and possible tissue grafting.
Further Outpatient Care
- Monitor patients for development of secondary infection; exclude other blistering dermatoses.
Complications
- Secondary infection and occasional scarring may occur.
- Osteomyelitis reportedly developed at a site of bullosis diabeticorum.
Prognosis
- Lesions often recur and secondary infection may develop, but the prognosis typically is good.
Patient Education
- For excellent patient education resources, visit eMedicine's Diabetes Center.
Medical/Legal Pitfalls
- Failure to recognize this entity may result in the overzealous treatment or systemic evaluations that may be required for similar conditions, such as porphyria or epidermolysis bullosa acquisita
| Media file 2:
Unroofed blister on the leg. Note the irregular shape. |
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Media type: Photo
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| Media file 3:
Histology of bullosis diabeticorum showing a noninflammatory blister with a subepidermal and focally intraepidermal separation (hematoxylin and eosin stain). |
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Media type: Photo
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| Media file 4:
High-power view of the dermis beneath the blister showing capillary wall thickening (hematoxylin and eosin stain). |
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Media type: Photo
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- Basarab T, Munn SE, McGrath J, et al. Bullosis diabeticorum. A case report and literature review. Clin Exp Dermatol. May 1995;20(3):218-20. [Medline].
- Bernstein JE, Levine LE, Medenica MM, et al. Reduced threshold to suction-induced blister formation in insulin- dependent diabetics. J Am Acad Dermatol. Jun 1983;8(6):790-1. [Medline].
- Bernstein JE, Medenica M, Soltani K, Griem SF. Bullous eruption of diabetes mellitus. Arch Dermatol. Mar 1979;115(3):324-5. [Medline].
- Cantwell AR Jr, Martz W. Idiopathic bullae in diabetics. Bullosis diabeticorum. Arch Dermatol. Jul 1967;96(1):42-4. [Medline].
- Centers for Disease Control and Prevention. National Diabetes Fact Sheet. United States. Available at: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2003.pdf. Atlanta, Ga: Centers for Disease Control and Prevention; 2003. [Full Text].
- Goodfield MJ, Millard LG, Harvey L, Jeffcoate WJ. Bullosis diabeticorum. J Am Acad Dermatol. Dec 1986;15(6):1292-4. [Medline].
- James WD, Odom RB, Goette DK. Bullous eruption of diabetes mellitus. A case with positive immunofluorescence microscopy findings. Arch Dermatol. Oct 1980;116(10):1191-2. [Medline].
- Kramer DW. Early or warning signs of impending gangrene in diabetes. Med J Rec. 1930;132:338-42.
- Toonstra J. Bullosis diabeticorum. Report of a case with a review of the literature. J Am Acad Dermatol. Nov 1985;13(5 Pt 1):799-805. [Medline].
- Tunuguntla A, Patel KN, Peiris AN, Zakaria WN. Bullosis diabeticorum associated with osteomyelitis. Tenn Med. Nov 2004;97(11):503-4. [Medline].
Bullous Disease of Diabetes excerpt Article Last Updated: Jun 28, 2006
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