Content of Hemorrhagic Bullae
Hemorrhagic bullae contain blood-filled fluid, which may include whole blood, serum mixed with red blood cells, and in certain contexts, mast cell mediators or bacterial organisms depending on the underlying etiology.
Composition Based on Underlying Pathology
Autoimmune Bullous Disease (Bullous Pemphigoid)
- The fluid in bullous pemphigoid consists of serum with inflammatory cells, particularly eosinophils, which accumulate in the subepidermal space 1, 2
- When hemorrhagic, these bullae contain blood mixed with serous fluid due to disruption of dermal blood vessels during the separation of the epidermis from the dermis 1
- The presence of eosinophilic infiltrate around blood vessels is characteristic and can be identified on histopathology 2
Cutaneous Mastocytosis
- In diffuse cutaneous mastocytosis (DCM), hemorrhagic bullae contain chondroitin sulfate, which acts as a local anticoagulant and contributes to the hemorrhagic nature 3
- Additional mast cell mediators found in blister fluid include platelet-activating factor (PAF), prostaglandin D2 (PGD2), and histamine 3
- These mediators are released from degranulating mast cells and contribute to both the hemorrhagic nature and associated symptoms 3
Infectious Causes (Necrotizing Fasciitis)
- In necrotizing fasciitis with hemorrhagic bullae, the fluid contains blood mixed with bacterial organisms, most commonly Vibrio species or Streptococcus pyogenes 4
- The hemorrhagic component results from obliterative endarteritis causing vessel thrombosis and tissue necrosis 5
- Gram stain and culture of the bullous fluid can demonstrate organisms directly, confirming blood-borne infection 6
Septicemia-Related Bullae
- In cases of gram-negative septicemia (such as Morganella morganii), hemorrhagic bullae contain blood with demonstrable organisms on Gram stain and culture 6
- The acral location and presence of organisms suggest direct blood-borne infection as the mechanism 6
Clinical Significance of Bullous Content
Diagnostic Implications
- Clear versus hemorrhagic fluid helps differentiate between early autoimmune disease (typically clear initially) and infectious/vascular causes (hemorrhagic from onset) 1, 4
- The presence of organisms on Gram stain from bullous fluid is pathognomonic for infectious etiology and mandates immediate aggressive treatment 4, 6
- Mast cell mediators in fluid confirm mastocytosis-related bullae, though this is primarily a pediatric presentation 3
Critical Pitfall
- Never assume hemorrhagic bullae are benign: in one prospective study, 100% of patients presenting to the emergency department with hemorrhagic bullae had necrotizing fasciitis, with 19% mortality 4
- The hemorrhagic nature indicates vascular compromise or thrombosis, which distinguishes life-threatening conditions from benign autoimmune disease 5, 4