Current concepts underlying the pathophysiology of acute Charcot neuroarthropathy in the diabetic foot and ankle

ABSTRACT

Introduction

With a complex and often misunderstood etiology, acute Charcot neuroarthropathy (ACN) is a devastating complication of peripheral neuropathy. In patients with diabetes, timely diagnosis of ACN in the foot and ankle is essential to prevent loss of both limb and life.

Areas covered

Herein, the authors evaluate the growing body of evidence in identifying targeted pathways for future therapeutic interventions. A literature search was conducted through the PubMed research database. Searched terms included ‘Charcot,’ ‘foot and ankle,’ ‘neuroarthropathy,’ ‘pathophysiology,’ ‘arthropathy,’ ‘diabetic foot,’ and ‘Charcot foot.’

Expert opinion

The interplay between the acute inflammatory response, cytokine signaling, and bone metabolism equilibrium can now be better understood with the aid of several novel immunobiologic mechanisms. The more recently elucidated roles of advanced glycation end-products, neuropeptides, monocyte differentiation, and genomics combine with classical Charcot pathophysiology to aid researchers and clinicians alike in combatting this often puzzling consequence of peripheral neuropathy.

KEYWORDS:

• Ankle
• diabetic foot
• acute Charcot
• neuroarthropathy
• diabetic arthropathy
• inflammation

Article highlights

• There are far more numerous connections between bone metabolism and the inflammatory cycle than previously thought.

• IL-17E, advanced glycation end-products, and monocyte differentiation patterns are promising new avenues in CNA research.

• The expanding power of genomics analysis may have unearthed a genetic predisposition to developing acute CNA among patients with diabetic peripheral neuropathy.

• Clinical trials investigating the use of novel pharmacologic treatments for ACN are underway.

Declaration of interest

The research work of DK Agrawal is supported by research grants R01HL128063, R01HL144125 and R01HL147662 from the National Institutes of Health, USA. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.