Bullous Disease of Diabetes Workup

  • Author: Maureen B Poh-Fitzpatrick, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Mar 29, 2011
 

Approach Considerations

The clinical workup of bullous disease of diabetes (bullosis diabeticorum) is fairly straightforward. Approaches range from culture to skin biopsy in order to more clearly differentiate the condition from other clinically similar conditions and identify secondary infections that might require treatment.

Cultures are only warranted if secondary bacterial infections are suspected. If bullous disease of diabetes blister fluid is cloudy instead of clear, the clinician should consider excluding secondary bacterial infection with culture of the blister fluid.

Should a patient present with prominent involvement of the dorsal hands, evaluation of porphyrin levels is warranted. levels are normal in persons with bullous disease of diabetes. Elevated levels indicate porphyria cutanea tarda or another blistering porphyria. Individuals with end-stage renal disease may have mildly elevated plasma porphyrin levels, possibly contributing to the total pathogenesis of blister formation.

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Immunofluorescence

No primary immunologic abnormality is noted in bullous disease of diabetes. Although nonspecific capillary-associated immunoglobulin M and C3 have been reported, albeit rarely,[8] immunofluorescence findings have not been consistently reproduced by others, and direct immunofluorescence findings are usually negative.[9] However, immunofluorescence studies may be required to exclude clinically similar conditions (eg, bullous pemphigoid, epidermolysis bullosa acquisita, porphyrias) that typically show deposition of C3 and immunoglobulin G along the basement membrane zone.

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Skin Biopsy and Histologic Findings

Shave biopsy or excisional/incisional biopsy can help to help distinguish bullous disease of diabetes from clinically similar conditions. For routine histologic sections, the clinician should include the blister and portions of the underlying dermis in the biopsy specimen and submit it in formalin.

Histologic features of bullous disease of diabetes are not entirely specific; lesions have a heterogeneous histologic presentation. Many of the reported cases describe a separation in the superficial epidermis within the superficial part of the spinous layer.

The blister plane may also appear in a subcorneal, intraepidermal, or subepidermal location; electron microscopy of fresh blisters has revealed separation in a subepidermal location, residing in the lamina lucida or the sublamina densa.[10] Anchoring fibrils and hemidesmosomes are reported absent or decreased in early blisters (see the image below).

Histology of bullosis diabeticorum showing a noninHistology of bullosis diabeticorum showing a noninflammatory blister with a subepidermal and focally intraepidermal separation (hematoxylin and eosin stain).

Note that the variable blister plane may be 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. Acantholysis is absent. Dermal changes (eg, capillary wall thickening, dermal sclerosis) may reflect the patient's underlying diabetes mellitus (see the image below). Caterpillar bodies typical of porphyria have been reported in lesions of bullous disease of diabetes.

High-power view of the dermis beneath the blister High-power view of the dermis beneath the blister showing capillary wall thickening (hematoxylin and eosin stain).
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Contributor Information and Disclosures
Author

Maureen B Poh-Fitzpatrick, MD  Professor Emerita of Dermatology and Special Lecturer, Columbia University College of Physicians and Surgeons; Professor of Medicine (Dermatology), University of Tennessee Health Science Center College of Medicine

Maureen B Poh-Fitzpatrick, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and New York Academy of Medicine

Disclosure: Lundbeck, Inc. Honoraria Review panel membership; Clinuvel Pharmaceuticals, Ltd. Honoraria Consulting

Coauthor(s)

Jacqueline M Junkins-Hopkins, MD  Associate Professor, Director, Division of Dermatopathology and Oral Pathology, Department of Dermatology, Johns Hopkins Medical Institutions

Jacqueline M Junkins-Hopkins, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and American Society of Dermatopathology

Disclosure: Nothing to disclose.

Specialty Editor Board

Maureen B Poh-Fitzpatrick, MD  Professor Emerita of Dermatology and Special Lecturer, Columbia University College of Physicians and Surgeons; Professor of Medicine (Dermatology), University of Tennessee Health Science Center College of Medicine

Maureen B Poh-Fitzpatrick, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and New York Academy of Medicine

Disclosure: Lundbeck, Inc. Honoraria Review panel membership; Clinuvel Pharmaceuticals, Ltd. Honoraria Consulting

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Edward F Chan, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine

Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

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

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

  1. Kramer DW. Early or warning signs of impending gangrene in diabetes. Med J Rec. 1930;132:338-42.

  2. Rocca FF, Pereyra E. Phlyctenar lesions in the feet of diabetic patients. Diabetes. May-Jun 1963;12:220-2. [Medline].

  3. Cantwell AR Jr, Martz W. Idiopathic bullae in diabetics. Bullosis diabeticorum. Arch Dermatol. Jul 1967;96(1):42-4. [Medline].

  4. Bernstein JE, Levine LE, Medenica MM, Yung CW, Soltani K. Reduced threshold to suction-induced blister formation in insulin-dependent diabetics. J Am Acad Dermatol. Jun 1983;8(6):790-1. [Medline].

  5. Larsen K, Jensen T, Karlsmark T, Holstein PE. Incidence of bullosis diabeticorum--a controversial cause of chronic foot ulceration. Int Wound J. Oct 2008;5(4):591-6. [Medline].

  6. Tunuguntla A, Patel KN, Peiris AN, Zakaria WN. Bullosis diabeticorum associated with osteomyelitis. Tenn Med. Nov 2004;97(11):503-4. [Medline].

  7. Lipsky BA, Baker PD, Ahroni JH. Diabetic bullae: 12 cases of a purportedly rare cutaneous disorder. Int J Dermatol. Mar 2000;39(3):196-200. [Medline].

  8. 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].

  9. Basarab T, Munn SE, McGrath J, Russell Jones R. Bullosis diabeticorum. A case report and literature review. Clin Exp Dermatol. May 1995;20(3):218-20. [Medline].

  10. 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].

  11. [Guideline] Bantle JP, Wylie-Rosett J, Albright AL, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care. Jan 2008;31 Suppl 1:S61-78. [Medline].

  12. [Guideline] American Diabetes Association. Standards of medical care in diabetes. I. Classification and diagnosis. Diabetes Care. Jan 2008;31(Suppl 1):S12-3.

  13. [Guideline] American Diabetes Association. Standards of medical care in diabetes. V. Diabetes care. Diabetes Care. Jan 2008;31(Suppl 1):S16-24.

  14. Bernstein JE, Medenica M, Soltani K, Griem SF. Bullous eruption of diabetes mellitus. Arch Dermatol. Mar 1979;115(3):324-5. [Medline].

  15. Centers for Disease Control and Prevention. National Diabetes Fact Sheet. United States. Atlanta, Ga: Centers for Disease Control and Prevention; 2003:[Full Text].

  16. Goodfield MJ, Millard LG, Harvey L, Jeffcoate WJ. Bullosis diabeticorum. J Am Acad Dermatol. Dec 1986;15(6):1292-4. [Medline].

  17. Phillips P, Weightman W. Diabetes and the skin. Correspondence. Aust Fam Physician. Oct 2005;34(10):48.

  18. Scheinfeld N. A review and report of blistering distal dactylitis due to Staphylococcus aureus in two HIV-positive men. Dermatol Online J. May 1 2007;13(2):8. [Medline]. [Full Text].

 
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Tense noninflammatory bulla on the leg.
Unroofed blister on the leg. Note the irregular shape.
Histology of bullosis diabeticorum showing a noninflammatory blister with a subepidermal and focally intraepidermal separation (hematoxylin and eosin stain).
High-power view of the dermis beneath the blister showing capillary wall thickening (hematoxylin and eosin stain).
 
 
 
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