Small Fibers Affected in Chronic Inflammatory Demyelinating Neuropathy

Patients with stable CIDP have significantly reduced IENFDS in distal leg and forearm compared with healthy individuals.

In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), the involvement of epidermal nerve fibers has been observed, according to study findings published in the journal Muscle & Nerve.

Researchers sought to quantify small fiber involvement in a mixed cohort of patients with typical CIDP and CIDP variants, in an effort to assess associations with clinical outcome measures at various stages of the disease. It is well known that although CIDP affects mainly large myelinated nerves, skin biopsy findings have suggested that intraepidermal nerve fiber densities (IEFNDs) are decreased as well.

Patients who had been followed between 2016 and 2019 at the Neuromuscular Unit of Istanbul University, Istanbul Faculty of Medicine, Turkey, who met the 2020 European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) clinical and electrophysiological diagnostic criteria for CIPD, were recruited for this study regardless of treatment status. Since the EFNS/PNS CIDP guidelines were revised in 2021, data from all of the patients recruited were reviewed to ensure their adherence to the revised criteria.

All patients were categorized as having “typical CIDP” or “CIDP variants.” Typical CIDP was defined as “progressive or relapsing, symmetric, proximal and distal muscle weakness of upper and lower limbs, and sensory involvement of at least [2] limbs with absent or reduced tendon reflexes in all limbs developing over at least 8 weeks.” Patients were classified as having “distal CIDP” if they experienced distal sensory loss and muscle weakness predominantly in the lower limbs. Individuals who experienced sensory loss and muscle weakness in a multifocal pattern, usually asymmetric, upper limb predominant, in >1 limb were classified as having “multifocal CIDP.”

Larger studies are needed to explore longitudinal changes in IEFND in CIDP and [their] relation to disease stage.

Other CIDP variants (ie, focal, motor, or sensory CIDP) were not included in the current study — either because they were reported infrequently in the study cohort or they did not meet the inclusion criteria of the study.

Skin punch biopsies were used to evaluate IEFNDs in 23 participants with CIDP and 13 healthy control individuals. Samples were obtained from the forearm, the thigh, and the distal leg. These skin sections were optimally interpreted in all 3 regions in 16 patients with CIDP and 10 age-matched/sex-matched healthy control individuals.

Functional disability was measured with the Inflammatory Neuropathy Cause and Treatment (INCAT; range, 0 to 10) and the Medical Research Council sum score evaluating 6 pairs of muscles (range, 0 to 60).

Disease activity was assessed via use of the CIDP Disease Activity Status (CDAS). Those participants whose CDAS status was classified as “remission” (ie, stable without treatment for <5 years); “stable active disease” (ie, stable with a treatment for >1 year); or “improvement” (ie, stable with treatment for >3 months but <1 year) were grouped as “stable CIDP.” Those whose disease status was classified as “unstable active disease” were classified as “unstable CIDP.” In other words, the patients who experienced their last CIDP attack within the past 3 months were grouped as “unstable CIDP,” whereas the other individuals were grouped as “stable CIDP.”

The researchers found that IEFNDs in the forearm, the thigh, and the distal leg were similar among 7 patients with typical CIDP and 9 individuals with CIDP variants. The IEFNDs in these 3 regions were reduced significantly in CIDP compared with healthy control individuals, demonstrating a moderate negative correlation with the INCAT Upper Limb Functional Disability Scores. Correlations for interobserver reliability for epidermal nerve fiber density were strong (CI, 0.875 to 0.921; P ≤.001), which were consistent with good interobserver agreement.

Reduction in IEFNDs, compared with healthy control individuals, was more pronounced in the distal leg. In patients with CIDP who were clinically unstable, IEFNDs of the distal leg and the forearm were reduced significantly compared with those with stable CIDP and the controls. Additionally, patients with CIDP who were clinically stable exhibited significantly reduced IEFNDs in the distal leg and the forearm compared with healthy control individuals.

The IEFNDs in all 3 regions demonstrated strong or very strong positive correlations with each other (distal leg with thigh, P =.001; distal leg with forearm, P <.0001; thigh with forearm, P <.0001). In fact, the IEFNDs in all 3 regions demonstrated moderate correlations with the INCAT disability scores of the upper extremity (forearm, P =.03; thigh, P =.046; distal leg, P =.034).

Several limitations of the present study should be noted. To begin, only a small number of patients with CIDP gave their consent for a skin biopsy, thus creating a sampling bias. Further, although no statistically significant difference was reported in the demographics between the patients and the healthy control individuals, those in the control group were younger than the CIDP patient cohort, which also might have influenced the study results.

The authors concluded by clarifying that “Larger studies are needed to explore longitudinal changes in IEFND in CIDP and [their] relation to disease stage.”

Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.  


Acarli ANÖ, Ünverengil G, Şirin NG, Çakar A, Durmuş H, Parman Y. Disease activity in chronic inflammatory demyelinating polyneuropathy: a comparative study of clinical and skin biopsy markers. Muscle Nerve. Published online September 23, 2022. doi:10.1002/mus.27726