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A 100-year-old black woman with diabetes was brought to the office by her family concerned about the large blister on her leg that started earlier that day (Figure 191-1). This large bulla appeared spontaneously without trauma, and there was no surrounding erythema. The bulla contained clear fluid, and there were no signs of infection. The bulla was drained with a sterile needle and no further bullae developed. The diagnosis is bullosis diabeticorum, a benign self-limited condition.

FIGURE 191-1

Bullosis diabeticorum on the lower leg of an older black woman with diabetes. This large bulla appeared spontaneously without trauma and there is no surrounding erythema. The bulla contained clear fluid and there was no infection. (Reproduced with permission from Richard P. Usatine, MD.)


Bullae are fluid-filled lesions on the skin that are larger than 10 mm in diameter. Bullous diseases are defined by the presence of bullae and vesicles (less than 10 mm in diameter). Bullous diseases are caused by many factors, including infections, bites, drug reactions, inflammatory conditions, and genetic and autoimmune diseases.


The approach to a patient with a blistering disorder begins with a complete history and physical examination. To make the final diagnosis, laboratory investigations or tissue biopsies may be needed.



  • How did the eruption present?

  • Has it changed in morphology or location?

  • Has it responded to any therapies?

  • Are there any associated symptoms or aggravating factors?

  • How has it impacted the patient's life?

  • Does the patient have any chronic medical conditions?

  • Does the patient take any medications?

  • Does the patient have any significant family history?


  • Note the location of the eruption.

  • Are the bullae flaccid or tense (Figure 191-2)?

  • Are there other lesions present (erosions, excoriations, papules, wheals)?

  • Is Nikolsky sign positive or negative? (Does the skin shear off when lateral pressure is applied to unblistered skin?)

  • Is Asboe-Hansen sign positive or negative (Figure 191-3)? (Do the bullae extend to surrounding skin when vertical pressure is applied?) Sometimes the Asboe-Hansen sign is also attributed to Nikolsky and called a Nikolsky sign, too.

  • Is the Darier sign positive or negative? (Do wheals form with rubbing of the skin?)

  • Note the skin background (sun-exposed skin, postinflammatory hyperpigmentation, lichenification, and scarring).

  • Does the patient have lymphadenopathy or hepatosplenomegaly?

FIGURE 191-2

Comparison of the tense bullae seen in bullous pemphigoid and the more flaccid bullae seen in pemphigus. A. Tense bullae in bullous pemphigoid. B. Flaccid bulla on the leg of a patient with pemphigus foliaceus. (Reproduced with permission from Richard P. Usatine, MD.)

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