Published: 7 March 2024

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Drug-induced phospholipidosis

Published 7 March 2024
Prescriber Update 45(1): 18–19
March 2024

The hydroxychloroquine (Plaquenil) data sheet was recently updated to include warnings for drug-induced phospholipidosis. This article provides information about the disorder.

What is drug-induced phospholipidosis?

Drug-induced phospholipidosis (DIPL) is a lysosomal storage disorder.^1,2 Lysosomes are cellular structures containing enzymes that break down proteins, nucleic acids, carbohydrates and lipids.³ A phospholipid membrane encloses the lysosome and maintains the acidic environment for the enzymes to function.³ In lysosomal storage disorders, undegraded material accumulates within the lysosomes of affected individuals.³

In DIPL, the inducing medicine causes lysosomal changes that lead to excessive but reversible accumulation of both phospholipids and the medicine in the lysosomes and the formation of lysosomal lamellar bodies.^1,2 They are called lamellar bodies due to the concentric ring shape seen on electron microscopy.¹ Given that nearly all cells contain lysosomes, and phospholipids are found in lysosome membranes, DIPL can affect any cell or organ in the body.¹

DIPL onset may or may not be associated with clinical symptoms, including inflammatory reactions and histopathological changes, such as macrophagic infiltration or fibrosis.^1,3 DIPL has been associated with organ toxicity, including of the heart, skeletal muscle, liver, lungs and kidneys.¹

Mechanism

The exact mechanism of DIPL is not known, although there are two hypotheses. The first assumes that the suspect medicine binds directly to phospholipids, creating a drug-lipid complex. The complex then accumulates to form the lysosomal lamellar bodies. The second hypothesis suggests that medicines interact and inhibit phospholipase activity, resulting in an accumulation of phospholipids.^1,4

Associated medicines

Over 50 medicines are associated with phospholipidosis. Examples of medicines with reports of clinically significant DIPL include:

• amiodarone¹
• fluoxetine¹
• gentamicin¹
• hydroxychloroquine⁵
• perhexiline¹

Treat patients presenting with signs and symptoms of organ toxicity as per local clinical guidelines. If DIPL is suspected, discontinue the suspect medicine.

References

1. Anderson N and Borlak J. 2006. Drug-induced phospholipidosis. FEBS Letters 580(23): 5533-40. DOI: 10.1016/j.febslet.2006.08.061 (accessed 16 January 2024).
2. Breiden B and Sandhoff K. 2020. Emerging mechanisms of drug-induced phospholipidosis. Biological Chemistry 401(1): 31-46. DOI: 10.1515/hsz-2019-0270 (accessed 17 January 2024).
3. Cooper GM. 2000. The Cell: A Molecular Approach (2nd edition). Sunderland (MA): Sinauer Associates. Available from: www.ncbi.nlm.nih.gov/books/NBK9953/ (accessed 5 February 2024).
4. Larson A. 2023. Drug-induced liver injury. In: UpToDate 14 April 2023. URL: www.uptodate.com/contents/drug-induced-liver-injury (accessed 17 January 2024).
5. Pharmacy Retailing Limited. 2023. Plaquenil New Zealand Data Sheet 18 December 2023. URL: www.medsafe.govt.nz/profs/datasheet/p/Plaqueniltab.pdf (accessed 17 January 2024).