Skin biopsy as a potential biomarker for chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare acquired autoimmune disorder with an orchestrated attack against the peripheral nervous system. Patients with typical CIDP present with proximal weakness, distal sensory deficit, and reduced or absent reflexes, which develop at least over 8 weeks. In the real-world, only 60-70% of patients will present with a classical CIDP phenotype, and atypical presentations with pure motor, focal, multifocal, or distal CIDP are common. CIDP is considered responsive to glucocorticoids, immunoglobulin, plasmapheresis, and neonatal Fc receptor inhibitors. However, treatment response can vary, and a prolonged course of treatment over the years is often necessary to keep the disease under control. The heterogeneity in clinical presentation and treatment response has made an accurate diagnosis of CIDP challenging, and apart from gross clinical outcome measures, there are no direct methods to assess treatment response. The EAN/PNS diagnostic criteria for CIDP is based on electrodiagnostic findings for demyelination and is highly specific for CIDP but may lack sensitivity in the real-world setting. Furthermore, electrodiagnostic studies are not a sensitive tool to assess treatment response. Nerve biopsy can help detect inflammation and demyelination, but given the invasive nature of the procedure, and permanent loss of sensation in the respective area after nerve biopsy, it is not recommended in routine cases. There have been scattered efforts to identify a blood biomarker for CIDP, but so far, no established validated blood biomarker for CIDP has been found. The absence of a validated and reliable diagnostic biomarker, which can be easily applied in the clinical setting, is a major obstacle in improving clinical care in CIDP. Skin punch biopsy is a minimally invasive tool routinely performed in the outpatient clinic and widely used to diagnose small fiber neuropathy. Recent studies have shown that skin biopsy can help detect neuropathy early in hereditary ATTR amyloid neuropathy and assess treatment response. Similarly, the observation that phosphorylated α-Synuclein can be detected in skin biopsies in over 90% of patients with synucleopathies, has essentially revolutionized the diagnosis of synucleopathies. Our previous work has shown that the density of intrapapillary myelinated endings (IME) that innervate Meissner corpuscles (MCs) is reduced in patients with diabetes mellitus in skin biopsy and quantified loss of myelinated nerve fibers correlate with nerve conduction study findings. We also have shown segmental demyelination in skin biopsy in patients with CIDP. However, the utility of skin biopsy in CIDP remains vastly unexplored, and a comprehensive study of skin biopsy changes in CIDP may lead to the development of an easily applicable biomarker of CIDP, which is potentially capable of detecting treatment response. Project Number: 1R21NS146830-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Bhaskar Roy | Institution: YALE UNIVERSITY, NEW HAVEN, CT | Award Amount: $246,574 | Activity Code: R21 | Study Section: Special Emphasis Panel[ZRG1 CN-Q (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11295151