Bullous disease of diabetes (bullosis diabeticorum) is a distinct, spontaneous, noninflammatory, blistering condition of acral skin that is unique to patients with diabetes mellitus.
Kramer first reported bullous-like lesions in diabetic patients in 1930  ; Rocca and Pereyra first characterized this as a phlyctenar (appearing like a burn-induced blister) in 1963.  Cantwell and Martz are credited with naming the condition bullosis diabeticorum in 1967.  It is also termed bullous disease of diabetes and diabetic bullae.
Bullous disease of diabetes tends to arise in long-standing diabetes or in conjunction with multiple complications. Prominent acral accentuation of bullous disease of diabetes lesions suggests a susceptibility to trauma-induced changes, but the definitive explanation awaits elucidation. (See Etiology.)
In the United States, Bullous disease of diabetes has been reported to occur in approximately 0.5% of diabetic patients. Male patients have twice the risk as female patients. (See Epidemiology.)
While lesions typically heal spontaneously within 2-6 weeks, they often recur in the same or different locations. Secondary infections may also develop; these are characterized by cloudy blister fluid and require a culture. (See Clinical Presentation.)
The clinician should consider direct immunofluorescence studies to exclude histologically similar entities (eg, noninflammatory bullous pemphigoid, epidermolysis bullosa acquisita, porphyria cutanea tarda, other bullous porphyrias). (See Workup.) Pseudoporphyria blistering due to photosensitizing drugs, chronic dialysis regimens, or ultraviolet A tanning devices should also be considered.
Specific treatment is unwarranted unless secondary infections (i.e. staphylococcal) occur, thereby warranting antibiotic therapy. However, aspiration of fluid from lesions using a small-bore needle might help prevent accidental rupture. (See Treatment and Management.)
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The pathophysiology of bullous disease of diabetes (bullosis diabeticorum) is likely multifactorial. Patients with diabetes have been shown to have a lower threshold for suction-induced blister formation compared with nondiabetic controls,  and because of the acral prominence of diabetic bullae, the role of trauma has been speculated.
Electron microscopic evidence has also suggested an abnormality in anchoring fibrils. However, this alone does not explain the often spontaneous development of multiple lesions at several locations.
In some patients, blisters are related to UV exposure, especially in those with nephropathy. Poor blood glucose regulation (hypoglycemia  and hyperglycemia  , or widely varying levels [5, 6] ), has been associated with blister formation.
The etiology of bullous disease of diabetes (bullosis diabeticorum) is unknown. Prominent acral accentuation of bullous disease of diabetes lesions suggests a susceptibility to trauma-induced changes, but the definitive explanation awaits elucidation.
Many, but not all, patients with bullous disease of diabetes 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. In some, especially in patients with neuropathy, UV exposure is also thought to play a role.  The postulated importance of glycemic control remains to be confirmed.
Bullous disease of diabetes (bullosis diabeticorum) tends to arise in patients with long-standing diabetes mellitus or with multiple complications of the disease. In the United States, bullous disease of diabetes has been reported to occur in approximately 0.5% of diabetic patients, although its frequency may actually be higher due to underreporting of blistering. Patients with uncomplicated or newly diagnosed disease, including type 2 diabetes, may also be affected.
The age of onset of bullous disease of diabetes ranges from 17 to 84 years, and the condition has been reported to be twice as prevalent in men as in women.
Bullous disease of diabetes (bullosis diabeticorum) blisters typically heal spontaneously, within 2-6 weeks, but lesions often recur in the same or a different location. Although secondary infection may develop, the prognosis for bullous disease of diabetes is typically good.
Although bullous disease of diabetes lesions often heal without significant scarring, they may be recurrent and also may lead to ulceration.  There have also been reports of osteomyelitis arising at a site of bullous disease of diabetes  and reports of amputation due to infection. 
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