What Causes Bullae?

Patient Presentation
A 7-month-old male came to clinic with a severe diaper rash that had begun 2 days before. His mother said that it looked like a normal diaper rash and she was treating it with large amounts of zinc-based barrier creams but it was not improving. During the morning she had changed his diaper and thought that it was looking a beefier-red than before. About 1 hour later she changed him again and there were large fluid filled blisters on his buttocks cheeks. She was afraid she would break the blisters so she just took a picture with her cellphone, re-diapered him and called the clinic for an appointment. She denied using any other soaps/lotions/detergents. He was not taking any medicine except that she had given him some acetaminophen as his buttocks seemed painful. He was eating and drinking well and had not had a fever, diarrhea or emesis. The past medical history revealed general dry skin. The review of systems was otherwise normal.

The pertinent physical exam showed a well-appearing male with normal vital signs. His skin examination showed 4-5 cm open raw lesions centered on the buttock cheeks. There were no blisters but denuded skin could be seen. The area was generally bright red and there appeared to be some elevation of another area near the denuded skin on the right buttock. There were no satellite lesions and the intertrigenous areas were not affected. He had mildly reddened skin on his forearms and behind his knees but no blisters or crusting. The mother’s pictures looked like flaccid bullae. The laboratory evaluation of a culture of the area eventually grew Streptococcus. The diagnosis of bullous impetigo was made and the patient was started on cephalexin. Silvadene® cream was also prescribed and the patient had resolution within a few days.

Bullae are fluid-filled epidermal lesions that are filled with serous or seropurulent fluid. They are > 1 cm in diameter and often easily rupture due to their thin walls. The differential diagnosis is different for bullae than for vesicular lesions with bullae being often more worrisome. However there is overlap and vesicular diseases can become large enough to be bullae. Drug toxicity and genetic problems are also more common in bullae whereas vesicles are more often caused by infectious diseases.

Potentially life threatening conditions such as toxic epidermal necrolysis syndrome, Stevens Johnson syndrome or meningococcemia need to be recognized and treated aggressively. Symptoms may include skin sloughing, petechiae or purpura, fever and irritability, inflammation of the mucosa, urticaria, respiratory distress, and diarrhea or abdominal pain. As bullae can cover extensive amounts of the skin and are often fragile, they may need specialized skin treatment with dermatology and burn specialists. Other supportive treatments such as fluid management, antibiotics and even respiratory support may be needed.

Vesicles are circumscribed, elevated, fluid-filled lesions < 1 cm in diameters on the skin. They contain serous exudates or a mixture of blood and serum. They last for a short time and either break spontaneously or evolve into bullae. They can be discrete (e.g. varicella or rickettsial disease), grouped (e.g. herpes), linear (e.g. rhus dermatitis) or irregular (e.g. coxsackie) in distribution.

A review and differential diagnosis of vesicles can be found here. Information about streptococcal diseases can be found here.

Learning Point

The differential diagnosis of bullae includes:

  • Trauma
    • Burns – including sunburn
    • Frostbite
    • Stings
  • Infection
    • Impetigo and Staphylococcal scalded skin syndrome
    • Herpes
    • Meningococcemia
    • Orf
    • Syphilis
  • Genetic
    • Acrodermatitis enteropathica
    • Epidermolysis bullosa
    • Incontinentia pigmenti
    • Porphyria
  • Other
    • Bullous disease of childhood
    • Drugs
    • Lupus erythematosis
    • Toxic epidermal necrolysis syndrome (TEN syndrome)
    • Pemphigus
    • Stevens Johnson syndrome

Questions for Further Discussion
1. What other disease entities are caused by Streptococcus?
2. What causes Stevens Johnson syndrome?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Streptococcal Infections.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Illingworth RS. Common Symptoms of Disease in Children. Blackwell Scientific Publications: Oxford. 1988:361-3.

Barr K. Evaluation of vesicular-bullous rash. ePocrates.
Available from the Internet at https://online.epocrates.com/u/2911775/Evaluation+of+vesicular-bullous+rash/Differential/Overview (rev.10/3/2014, cited 3/16/2015).


Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital