AA Amyloidosis as a Likely Cause of Bilateral Pleural Effusion in Epidermolysis Bullosa

We would like to highlight AA (secondary) amyloidosis as an important and often under-recognized cause of bilateral pleural effusion in patients with long-standing epidermolysis bullosa (EB).

Severe forms of EB are associated with chronic inflammation, recurrent infections, and persistent elevation of serum amyloid A (SAA). Over time, this can lead to AA amyloid deposition in multiple organs.

In such patients, pleural effusion may occur due to:

• Nephrotic syndrome from renal AA amyloid → hypoalbuminemia → transudative effusions
• Direct amyloid deposition in pleural surfaces
• Less commonly, cardiac involvement causing fluid overload

Key clinical clues supporting AA amyloidosis include:

• Long-standing inflammatory skin disease (EB)
• Proteinuria or renal dysfunction
• Hypoalbuminemia and edema
• Elevated inflammatory markers
• Unexplained bilateral pleural effusions

Diagnosis requires tissue confirmation (Congo red–positive amyloid) with amyloid typing to confirm AA subtype, while excluding AL amyloidosis.

Early recognition is crucial, as control of the underlying inflammation is the cornerstone of treatment and may stabilize or improve organ involvement. Supportive management alone (e.g., diuretics) is often insufficient if inflammation persists.

This case emphasizes that bilateral pleural effusion in EB should prompt active evaluation for AA amyloidosis.

We welcome discussion on:

• Diagnostic strategies in limited-resource settings
• Role of biologic therapies in AA amyloidosis
• Long-term outcomes in EB-associated amyloidosis