Peripheral neuropathic changes in pachyonychia congenita

Area of Science:

• Dermatology
• Neurology
• Genetics

Background:

• Pachyonychia congenita (PC) is a rare genetic disorder.
• Skin abnormalities in PC are primarily linked to keratin mutations.
• Neuropathic pain is a common symptom in PC patients.

Purpose of the Study:

• To compare nerve fiber and mechanoreceptor patterns in affected and unaffected plantar skin of PC patients and controls.
• To investigate potential mechanisms underlying neuropathic pain in PC.

Main Methods:

• Plantar skin biopsies from 10 PC patients (KRT6A mutation) and 10 controls.
• Analysis of intraepidermal nerve fibers (IENF), mechanoreceptors, blood vessels, and Merkel cells (MCs).
• Quantification using stereology and validated methods; assessment of pressure pain thresholds.

Main Results:

• PC-affected skin showed reduced sweat gland innervation and Meissner corpuscles.
• Increased Merkel cell densities and blood vessel counts were observed in PC-affected skin.
• Lower pressure pain thresholds were found in PC-affected skin compared to controls.

Conclusions:

• Skin innervation and mechanoreceptor alterations in PC extend beyond keratinocyte changes.
• These findings suggest potential targets for studying and managing neuropathic pain in PC.
• Callus formation alone does not significantly increase Merkel cell numbers.