Are You Confident of the Diagnosis?

A rare, confusing and controversial entity reportedly affecting 0.5% of diabetics. Is bullosis diabeticorum a specific condition?

What you should be alert for in the history

Rapid and spontaneous development of one to several blisters, typically on the feet or lower extremities, without identifiable history of antecedent trauma. Blisters heal rapidly with good wound care unless there is accompanying ulceration.

Characteristic findings on physical examination

One to multiple bullae of varying sizes on the lower legs and the dorsal and plantar surfaces of the feet–rarely on the hands, upper extremities or trunk. Blister fluid variable: clear and yellowish to “syrupy” or hemorrhagic.

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Expected results of diagnostic studies

Biopsy technique: punch or shave biopsy to include the blister and underlying skin from the blister edge. Histopathology is nonspecific. Changes are consistent with underlying diabetes: capillary wall hyalinization and dermal sclerosis. Level of blister separation is not consistent, most often subepidermal but also frequently intraepidermal or subcorneal. Different levels of cleavage are possibly due to rapid reepithelialization of the blister floor.

Electron microscopy: split at the dermal-epidermal junction in the sublamina densa. There have been conflicting reports of either intact or destroyed anchoring filaments and hemidesmosomes and negative immunofluoresence.

Blister fluid: culture negative.

Diagnosis confirmation

–Bullae, clear or hemorrhagic, associated with neuropathy (lack of sensation) over pressure points on the feet. Can appear rapidly with minimal or unidentified friction/pressure. Often located over bony prominences (Charcot foot). Distinguished by location and physical examination for diminished sensation and foot morphology

–Bullae associated with edema of the lower extremity and foot. Clinical edema with fluid accumulation and bullae formation.

–Burns: Distinguished by history of contact with hot utensils or heating pads. Often associated with poor vision in diabetic patients.

–Trauma: shear or pressure forces on insensate areas, usually on lower extremities.

–Bullous pemphigoid: Clinical presentation. Biopsy split in lamina lucida. Positive direct immunofluorescence–Porphyria cutanea tarda: Clinical presentation on hands. Elevated blood porphyrins. Biopsy changes

Who is at Risk for Developing this Disease?

Slight male predominance. Increased incidence of diabetic neuropathy and nephropathy.

What is the Cause of the Disease?

Pathophysiology of blister formation is not certain. The role of neuropathy with diminished sensation and trauma is likely important. A lower threshold for suction-induced blister formation is indicative of a possible traumatic component.

Systemic Implications and Complications

Most blisters heal with wound care and off-loading without complications. There are reports of secondary infection. Bullosis diabeticorum can precede the development of underlying neuropathic ulceration.

Treatment Options

Table 1 Treatment options are outlined in the Table.

Table 1.
Medical treatment – topical Moist wound care
Medical treatment – systemic
Surgical treatment Drainage of bullae, leaving roof as bandaid Sharp debridement of necrotic material
Physical treatment Off-loading of involved areas with shoewear, casting or felted foam

Optimal Therapeutic Approach for this Disease

Blisters are best managed conservatively with incision and drainage or aspiration of larger blisters to prevent rupture and loss of blister roof. Application of nonadherent dressings over topical ointment, petrolatum or antimicrobial, are dictated by culture. Foot protection and off-loading is valuable. Systemic antibiotics in selected cases are based on clinical and culture findings.

Patient Management

1 Decompress bulla with small incision. Leave the roof intact to act as a moist band-aid/dressing.

2. Maintain moist wound care with vaseline impregnated gauze over the site

3 Off load any pressure points. Ulceration over a pressure point on the plantar foot are best treated with a contact cast or the felted foam technique.

Unusual Clinical Scenarios to Consider in Patient Management

Bacterial infections are uncommon. Osteomyelitis has been associated with bullosis diabeticorum.

What is the Evidence?

Larsen, K, Jensen, T, Karlsmark, T, Holstein, PE. “Incidence of bullosis diabeticorum – a controversial cause of chronic foot ulceration”. Int Wound J. vol. 5. 2008. pp. 591-6. (Comprehensive review of bullosis diabeticorum with focus on diagnosis, treatment, and management strategies.)

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. vol. 8. 1983. pp. 790-1. (Study of 25 patients describing increased susceptibility to suction-induced blistering.)

Lipsky, BA, Baker, PD, Ahroni, JH. “Diabetic bullae: 12 cases of a purportedly rare cutaneous disorder”. Int J Dermatol. vol. 39. 2000. pp. 196-200. (Case series and review of patients with diabetic bullae with illustrations.)

Cantwell AR Jr, Martz, W. “Idiopathic bullae in diabetics: bullosis diabeticorum”. Arch Dermatol. vol. 96. 1967. pp. 42-4. (Review of diabetic bullae.)

Tunuguntla, A, Patel, KN, Peiris, AN, Zakaria, WN. “Bullosis diabeticorum associated with osteomyelitis”. Tenn Med. vol. 97. 2004. pp. 503-4. (Report of osteomyelitis found in patient with diabetic bullae.)

Derighetti, M, Hohl, D, Krayenbuhl, BH, Panizzon, RG. “Bullosis diabeticorum in a newly discovered type 2 diabetes mellitus”. Dermatology. vol. 200. 2000. pp. 366-7. (Case report of diabetic bullae found in a patient with newly diagnosed diabetes rather than history of long-standing diabetes.)

Toonstra, J. “Bullosis diabeticorum: Report of a case with review of the literature”. J Am Acad Dermatol. vol. 13. 1985. pp. 799-805. (Case report of one patient with bullosis diabeticorum with comprehensive review.)

Goodfield, MJD, Millard, LG, Harvey, L, Jeffcoate, WJ. “Bullosis diabeticorum. Correspondence”. J Am Acad Dermatol. vol. 15. 1986. pp. 1292-4. (Response to article by Toonstra et al with focus on histopathologic and electron microscopy findings.)

James, WD, Odom, RB, Goette, DK. “Bullous eruption of diabetes mellitus: A case with positive immunofluorescence microscopy findings”. Arch Dermatol. vol. 116. 1980. pp. 1191-2. (Discussion of positive immunofluorescence findings in a patient with bullosis diabeticorum.)